Association between positive blood culture and clinical outcomes among children treated for sepsis in the emergency department.

OBJECTIVE: Among children treated for sepsis in a pediatric emergency department (ED), compare clinical features and outcomes between those with blood cultures positive versus negative for a bacterial pathogen. DESIGN: Single-center retrospective cohort study. SETTING: Pediatric emergency department (ED) at a quaternary pediatric care center. PATIENTS: Children aged 0-18 years treated for sepsis defined by the Children's Hospital Association's Improving Pediatric Sepsis Outcomes (IPSO) definition. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 1307 patients treated for sepsis during the study period, of which 117 (9.0%) had blood cultures positive for a bacterial pathogen. Of children with blood culture positive sepsis, 62 (53.0%) had organ dysfunction compared to 514 (43.2%) with culture negative sepsis (adjusted odds ratio 1.56, 95% confidence interval (CI) 1.04-2.34, adjusting for age, high risk medical conditions, and time to antibiotics). Children with blood culture positive sepsis had a larger base deficit, -4 vs -1 (p < 0.01), and higher procalcitonin, 3.84 vs 0.56 ng/mL (p < 0.01). CONCLUSIONS: Children meeting the IPSO Sepsis definition with blood culture positive for a bacterial pathogen have higher rates of organ dysfunction than those who are culture negative, although our 9% rate of blood culture positivity is lower than previously cited literature from the pediatric intensive care unit.

Prevalence of Cardiac Dysfunction in Malawian Children With Severe Febrile Illness.

OBJECTIVES: To investigate the prevalence of left ventricular systolic dysfunction (LVSD) in Malawian children with severe febrile illness and to explore associations between LVSD and mortality and lactate levels. DESIGN: Prospective observational study. SETTING: Pediatric ward of a tertiary government referral hospital in Malawi. PATIENTS: Children between 60 days and 10 years old with severe febrile illness (fever with at least one sign of impaired perfusion plus altered mentation or respiratory distress) were enrolled at admission from October 2017 to February 2018. INTERVENTIONS: Focused cardiac ultrasound (FoCUS) was performed, and serum lactate was measured for each child at enrollment, with repeat FoCUS the following day. LV systolic function was later categorized as normal, reduced, severely reduced, or hyperdynamic by two pediatric cardiologists blinded to clinical course and outcomes. MEASUREMENTS AND MAIN RESULTS: Fifty-four children were enrolled. LVSD was present in 14 children (25.9%; 95% CI, 15.4-40.3%), of whom three had severely reduced function. Thirty patients (60%) had a lactate greater than 2.5 mmol/L, of which 20 (40%) were markedly elevated (>5 mmol/L). Ten children died during admission (18.5%). Of children who survived, 22.7% had decreased LV systolic function versus 40% of those who died. Dysfunction was not associated with mortality or elevated lactate. CONCLUSIONS: Cardiac dysfunction may be present in one in four Malawian children with severe febrile illness, and mortality in these patients is especially high. Larger studies are needed to further clarify the role cardiac dysfunction plays in mortality and integrate practical bedside assessments for decision support around individualized resuscitation strategies.

Patterns of Vasoactive Agent Initiation Among Children With Septic Shock in the Pediatric Emergency Department.

OBJECTIVE: The aim of the study was to describe patterns of initiation (and factors associated with delayed initiation) of vasoactive agents among pediatric emergency patients with septic shock. METHODS: Patients with septic shock from November 2013 to September 2016 who had a vasoactive agent initiated for documented hypotension were classified as "guideline adherent" (hypotensive following the final fluid bolus and had vasoactive agents initiated within 60 minutes) or "delayed initiation" (hypotensive after the final bolus and were initiated on vasoactive agents after >60 minutes). Patient-level factors (demographics, presence of underlying condition including central venous catheter, and markers of disease severity) and outcomes (mortality, length of stay) were compared between groups. RESULTS: Of the 37 eligible patients, 17 received vasoactive agents within "guideline adherent" timelines and 10 were "delayed initiation." An additional group was identified as "transient responders"; these patients were normotensive after a final fluid bolus but developed hypotension and were initiated on a vasoactive agent within 2 hours after admission (n = 10). We found no significant difference between the "guideline adherent" and "delayed initiation" groups according to patient-level factors or outcomes; "transient responders" were more likely than other groups to have a central venous catheter and had longer lengths of stay. CONCLUSIONS: Although there are perceived barriers to vasoactive agent initiation, we found no significant difference in patient-level factors between the timely and delayed groups. This study also identified a group of patients labeled as transient responders, who initially appeared volume responsive but who required vasoactive support within several hours. This cohort requires further study.

The Medical Resuscitation Committee: Interprofessional Program Development to Optimize Care for Critically Ill Medical Patients in an Academic Pediatric Emergency Department.

ABSTRACT: Provision of optimal care to critically ill patients in a pediatric emergency department is challenging. Specific challenges include the following: (a) patient presentations are highly variable, representing the full breadth of human disease and injury, and are often unannounced; (b) care team members have highly variable experience and skills and often few meaningful opportunities to practice care delivery as a team; (c) valid data collection, for quality assurance/improvement and clinical research, is limited when relying on traditional approaches such as medical record review or self-report; (d) specific patient presentations are relatively uncommon for individual providers, providing few opportunities to establish and refine the requisite knowledge and skill; and (e) unscientific or random variation in care delivery. In the current report, we describe our efforts for the last decade to address these challenges and optimize care delivery to critically ill patients in a pediatric emergency department. We specifically describe the grassroots development of an interprofessional medical resuscitation program. Key components of the program are as follows: (a) a database of all medical patients undergoing evaluation in the resuscitation suite, (b) peer review and education through video-based case review, (c) a program of emergency department in situ simulation, and (d) the development of cognitive aids for high-acuity, low-frequency medical emergencies.

Characterization of Children with Septic Shock Cared for by Emergency Medical Services.

Objective: To inform the future development of a pediatric prehospital sepsis tool, we sought to 1) describe the characteristics, emergent care, and outcomes for children with septic shock who are transported by emergency medicine services (EMS) and compare them to those self-transported; and 2) determine the EMS capture rate of common sepsis screening parameters and the concordance between the parameters documented in the EMS record and in the emergency department (ED) record. Methods: This is a retrospective cohort study of children ages 0 through 21 years who presented to a pediatric ED with septic shock between 11/2013 and 06/2016. Data, collected by electronic and manual chart review of EMS and ED records, included demographics, initial vital signs in both EMS and ED records, ED triage level, site of initial ED care, ED disposition, ED therapeutic interventions, outcomes, and times associated with processes. Potential screening parameters were dichotomized as normal vs. abnormal based on age-dependent normative data. Results: Of the children with septic shock treated in our ED, 19.3% arrived via EMS. These children as compared to those self-transported were more likely (i.e., p < 0.05) to be male, have public insurance, receive initial care in the ED resuscitation suite, be hypotensive on arrival, receive their first ED fluid bolus sooner (33 vs. 58 minutes), receive vasoactive agents, be mechanically ventilated in the first 24 hours, and have slightly longer length of hospital stays. Both groups had similar times to antibiotics. While poor outcomes were rare, the 3- and 30-day mortalities were similar for both groups. EMS capture rates were highest for heart rate and respiratory rate and lowest for temperature, glucose, and blood pressure. Interrater reliability was highest for heart rate. Conclusions: Children presenting to the ED with septic shock transported by EMS represent a critically ill subset of modest proportions. Realization of a sepsis screening tool for this vulnerable population will require both creation of a tool containing a limited subset of objective parameters along with processes to ensure capture.

Bubble CPAP and oxygen for child pneumonia care in Malawi: a CPAP IMPACT time motion study.

BACKGROUND: In some low-resource settings bubble continuous positive airway pressure (bCPAP) is increasingly used to treat children with pneumonia. However, the time required for healthcare workers (HCWs) to administer bCPAP is unknown and may have implementation implications. This study aims to compare HCW time spent administering bCPAP and low-flow nasal oxygen care at a district hospital in Malawi during CPAP IMPACT (Improving Mortality for Pneumonia in African Children Trial). METHODS: Eligible participants were 1-59 months old with WHO-defined severe pneumonia and HIV-infection, HIV-exposure, severe malnutrition, or hypoxemia and were randomized to either bCPAP or oxygen. We used time motion techniques to observe hospital care in four hour blocks during treatment initiation or follow up (maintenance). HCW mean time per patient at the bedside over the observation period was calculated by study arm. RESULTS: Overall, bCPAP required an average of 34.71 min per patient more than low-flow nasal oxygen to initiate (bCPAP, 118.18 min (standard deviation (SD) 42.73 min); oxygen, 83.47 min (SD, 20.18 min), p < 0.01). During initiation, HCWs spent, on average, 12.45 min longer per patient setting up bCPAP equipment (p < 0.01) and 11.13 min longer per patient setting up the bCPAP nasal interface (p < 0.01), compared to oxygen equipment and nasal cannula set-up. During maintenance care, HCWs spent longer on average per patient adjusting bCPAP, compared to oxygen equipment (bCPAP 4.57 min (SD, 4.78 min); oxygen, 1.52 min (SD, 2.50 min), p = 0.03). CONCLUSION: Effective bCPAP implementation in low-resource settings will likely create additional HCW burden relative to usual pneumonia care with oxygen. TRIAL REGISTRATION: Clinicaltrials.gov NCT02484183 , June 29, 2015.

A pediatric death audit in a large referral hospital in Malawi.

BACKGROUND: Death audits have been used to describe pediatric mortality in under-resourced settings, where record keeping is often a challenge. This information provides the cornerstone for the foundation of quality improvement initiatives. Malawi, located in sub-Saharan Africa, currently has an Under-5 mortality rate of 64/1000. Kamuzu Central Hospital, in the capital city Lilongwe, is a busy government referral hospital, which admits up to 3000 children per month. A study published in 2013 reported mortality rates as high as 9%. This is the first known audit of pediatric death files conducted at this hospital. METHODS: A retrospective chart review on all pediatric deaths that occurred at Kamuzu Central Hospital (excluding deaths in the neonatal nursery) during a 13-month period was done using a standardized death audit form. A descriptive analysis was completed, including patient demographics, HIV and nutritional status, and cause of death. Modifiable factors were identified that may have contributed to mortality, including a lack of vital sign collection, poor documentation, and delays in the procurement or results of tests, studies, and specialist review. RESULTS: Seven hundred forty three total pediatric deaths were recorded and 700 deceased patient files were reviewed. The mortality rate by month ranged from a low of 2.2% to a high of 4.4%. Forty-four percent of deaths occurred within the first 24 h of admission, and 59% occurred within the first 48 h. The most common causes of death were malaria, malnutrition, HIV-related illnesses, and sepsis. CONCLUSIONS: The mortality rate for this pediatric referral center has dramatically decreased in the 6 years since the last published mortality data, but remains high. Areas identified for continued development include improved record keeping, improved patient assessment and monitoring, and more timely and reliable provision of testing and treatment. This study demonstrates that in low-resource settings, where reliable record keeping is often difficult, death audits are useful tools to describe the sickest patient population and determine factors possibly contributing to mortality that may be amenable to quality improvement interventions.

Estimating the probability of bacterial infection using a novel biomarker among pediatric patients in the emergency department.

CONTEXT: IL-27 is a novel biomarker to identify bacterial infection in children. OBJECTIVE: IL-27 was evaluated among pediatric emergency department (ED) patients and compared with procalcitonin (PCT). METHODS AND RESULTS: Children undergoing blood, urine, or cerebrospinal fluid cultures had IL-27 and PCT assays performed. Bacterial infection was defined as a positive culture or a clinical diagnosis based on chart review. IL-27 and PCT were increased among patients with bacterial infection and demonstrated comparable AUC's (0.62 versus 0.61). A decision tree incorporating IL-27, PCT, and white blood cell count improved the AUC (0.80). CONCLUSION: IL-27 is a viable candidate biomarker to identify bacterial infection among ED patients and is comparable with PCT.

Opportunities for earlier HIV diagnosis in a pediatric ED.

OBJECTIVES: Emergency department (ED) HIV screening is recommended but challenging to implement and of uncertain effectiveness in pediatric EDs (PEDs). We sought to determine whether there were opportunities for earlier HIV diagnosis in the PED for a cohort of young adults diagnosed with HIV. METHODS: This retrospective cohort study reviewed PED records of a group of young adults receiving HIV care in an urban hospital setting. Pediatric ED visits were selected for review if they took place after the patient's estimated time of HIV acquisition and before their eventual diagnosis. Charts were reviewed to determine whether HIV infection was suspected and whether testing was offered. RESULTS: Among a cohort of HIV-positive young adults, only 3 (3.6%; 95% confidence interval, 0.9-10.8) of 84 were seen in the PED during the time they were undiagnosed but likely to be infected with HIV. Among these subjects, there was no documentation that HIV testing was offered or refused nor was there documented suspicion of HIV. CONCLUSIONS: There are opportunities for earlier diagnosis of HIV in PEDs, affirming the importance of HIV screening implementation in these settings. However, PEDs are unlikely to have the same frequency of contact with undiagnosed individuals as do adult EDs. Alternative methods of accessing at-risk adolescent populations must be identified.

Leukopenia, neutropenia, and procalcitonin levels in young febrile infants with invasive bacterial infections.

BACKGROUND AND OBJECTIVE: Serum procalcitonin (PCT) is a highly accurate biomarker for stratifying the risk of invasive bacterial infections (IBIs) in febrile infants ≤60 days old. However, PCT is unavailable in some settings. We explored the association of leukopenia and neutropenia with IBIs in non-critically ill febrile infants ≤60 days old, with and without PCT. METHODS: We conducted a secondary analysis of a prospective observational cohort consisting of 7407 non-critically ill infants ≤60 days old with temperatures ≥38°C. We focused on the risk of IBIs in patients with leukopenia (white blood cell [WBC] count <5000 cells/µL) or neutropenia (absolute neutrophil count [ANC] <1000 cells/µL), categorized to extremes of lower values, and the impact of PCT on these associations. Multiple logistic regression was used to identify independent predictors of IBIs. RESULTS: Final analysis included 6865 infants with complete data; 45% (3098) had PCT data available. Of the 6865, a total of 111 (1.6%) had bacteremia without bacterial meningitis, 18 (0.3%) had bacterial meningitis without bacteremia, and 19 (0.3%) had both bacteremia and bacterial meningitis. IBI was present in four of 20 (20%) infants with WBC counts ≤2500 cells/µL and four of 311 (1.3%) with ANC <1000 cells/µL. In multivariable logistic regression analysis not including PCT, a WBC count <2500 cells/µL was significantly associated with IBI (OR 13.48, 95% CI 2.92-45.35). However, no patients with leukopenia or neutropenia and PCT ≤0.5 ng/mL had IBIs. CONCLUSIONS: Leukopenia ≤2500 cells/µL in febrile infants ≤60 days old is associated with IBIs. However, in the presence of normal PCT levels, no patients with leukopenia had IBIs. While this suggests leukopenia ≤2500 cells/µL is a risk factor for IBIs in non-critically ill young febrile infants only when PCT is unavailable or elevated, the overall low frequency of leukopenia in this cohort warrants caution in interpretation, with future validation required.

Virtual Interviews and the Pediatric Emergency Medicine Match Geography: A National Survey.

Introduction: Virtual interviews (VI) are now a permanent part of pediatric emergency medicine (PEM) recruitment, especially given the cost and equity advantages. Yet inability to visit programs in person can impact decision-making, leading applicants to apply to more programs. Moreover, the cost advantages of VI may encourage applicants to apply to programs farther away than they might otherwise have been willing or able to travel. This could create unnecessary strain on programs. We conducted this study to determine whether PEM fellowship applicants would apply to a larger number of programs and in different geographic patterns with VI (2020 and 2021) as compared to in-person interviews (2018 and 2019). Methods: We conducted an anonymous national survey of all PEM fellows comparing two cohorts: current fellows who interviewed inperson (applied in 2018/2019) and fellows who underwent VIs in 2020/2021 (current fellows and those recently matched in 2021). The study took place in March-April 2022. Questions focused on geographic considerations during interviews and the match. We used descriptive statistics, chi-square and t-tests for analysis. Results: Overall response rate was 42% (231/550); 32% (n = 74) interviewed in person and 68% (n = 157) virtually. Fellows applied to a median of 4/6 geographic regions (interquartile range 2, 5). Most applied for fellowship both in the same region as residency (216, 93%) and outside (192, 83%). Only the Pacific region saw a statistically significant increase in applicants during VI (59.9% vs 43.2%, P = 0.02). There was no statistical difference in the number of programs applied to during in-person vs VI (mean difference (95% confidence interval 0.72, -2.8 - 4.2). A majority matched in their preferred state both during VI (60.4%) and in-person interviews (65.7%). The difference was not statistically significant (P = 0.45). Conclusion: While more PEM fellowship applicants applied outside the geographic area where their residency was and to the Pacific region, there was no overall increase in the number of programs or geographic areas PEM applicants applied to during VI as compared to in-person interview seasons. As this was the first two years of VI, ongoing data collection will further identify trends and the impactof VI.

Comprehensive assessment of pediatric acute and inpatient care at a tertiary referral hospital in Malawi: opportunities for quality improvement.

BACKGROUND: Despite the reduction in global under-5 mortality over the last decade, childhood deaths remain high. To combat this, there has been a shift in focus from disease-specific interventions to use of healthcare data for resource allocation, evaluation of performance and impact, and accountability. This is a descriptive analysis of data derived from a prospective cohort study describing paediatric admissions to a tertiary referral hospital in Malawi for the purpose of process evaluation and quality improvement. METHODS: Using a REDCap database, we collected data for patients admitted acutely to Kamuzu Central Hospital, a tertiary referral centre in the central region. Data were collected from 17 123 paediatric inpatients from 2017 to 2020. RESULTS: Approximately 6% of patients presented with either two or more danger signs or severely abnormal vital signs. Infants less than 6 months, who had the highest mortality rate, were also the most critically ill on arrival to the hospital. Sepsis was diagnosed in about 20% of children across all age groups. Protocols for the management of high-volume, lower-acuity conditions such as uncomplicated malaria and pneumonia were generally well adhered to, but there was a low rate of completion for labs, radiology studies and subspecialty consultations required to provide care for high acuity or complex conditions. The overall mortality rate was 4%, and 60% of deaths occurred within the first 48 hours of admission. CONCLUSION: Our data highlight the need to improve the quality of care provided at this tertiary-level centre by focusing on the initial stabilisation of high-acuity patients and augmenting resources to provide comprehensive care. This may include capacity building through the training of specialists, implementation of clinical processes, provision of specialised equipment and increasing access to and reliability of ancillary services. Data collection, analysis and routine use in policy and decision-making must be a pillar on which improvement is built.

Mortality by Admission Diagnosis in Children 1-60 Months of Age Admitted to a Tertiary Care Government Hospital in Malawi.

Diagnosis-specific mortality is a measure of pediatric healthcare quality that has been incompletely studied in sub-Saharan African hospitals. Identifying the mortality rates of multiple conditions at the same hospital may allow leaders to better target areas for intervention. In this secondary analysis of routinely collected data, we investigated hospital mortality by admission diagnosis in children aged 1-60 months admitted to a tertiary care government referral hospital in Malawi between October 2017 and June 2020. The mortality rate by diagnosis was calculated as the number of deaths among children admitted with a diagnosis divided by the number of children admitted with the same diagnosis. There were 24,452 admitted children eligible for analysis. Discharge disposition was recorded in 94.2% of patients, and 4.0% (N = 977) died in the hospital. The most frequent diagnoses among admissions and deaths were pneumonia/bronchiolitis, malaria, and sepsis. The highest mortality rates by diagnosis were found in surgical conditions (16.1%; 95% CI: 12.0-20.3), malnutrition (15.8%; 95% CI: 13.6-18.0), and congenital heart disease (14.5%; 95% CI: 9.9-19.2). Diagnoses with the highest mortality rates were alike in their need for significant human and material resources for medical care. Improving mortality in this population will require sustained capacity building in conjunction with targeted quality improvement initiatives against both common and deadly diseases.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Identifying modifiable risk factors for mortality in children aged 1-59 months admitted with WHO-defined severe pneumonia: a single-centre observational cohort study from rural Malawi.

OBJECTIVE: Although HIV infection, severe malnutrition and hypoxaemia are associated with high mortality in children with WHO-defined severe pneumonia in sub-Saharan Africa, many do not have these conditions and yet mortality remains elevated compared with high-resource settings. Further stratifying mortality risk for children without these conditions could permit more strategic resource utilisation and improved outcomes. We therefore evaluated associations between mortality and clinical characteristics not currently recognised by the WHO as high risk among children in Malawi with severe pneumonia but without HIV (including exposure), severe malnutrition and hypoxaemia. METHODS: Between May 2016 and March 2018, we conducted a prospective observational study alongside a randomised controlled trial (CPAP IMPACT) at Salima District Hospital in Malawi. Children aged 1-59 months hospitalised with WHO-defined severe pneumonia without severe malnutrition, HIV and hypoxaemia were enrolled. Study staff assessed children at admission and ascertained hospital outcomes. We compared group characteristics using Student's t-test, rank-sum test, χ2 test or Fisher's exact test as appropriate. RESULTS: Among 884 participants, grunting (10/112 (8.9%) vs 11/771 (1.4%)), stridor (2/14 (14.2%) vs 19/870 (2.1%)), haemoglobin <50 g/L (3/27 (11.1%) vs 18/857 (2.1%)) and malaria (11/204 (5.3%) vs 10/673 (1.4%)) were associated with mortality compared with children without these characteristics. Children who survived had a 22 g/L higher mean haemoglobin and 0.7 cm higher mean mid-upper arm circumference (MUAC) than those who died. CONCLUSION: In this single-centre study, our analysis identifies potentially modifiable risk factors for mortality among hospitalised Malawian children with severe pneumonia: specific signs of respiratory distress (grunting, stridor), haemoglobin <50 g/L and malaria infection. Significant differences in mean haemoglobin and MUAC were observed between those who survived and those who died. These factors could further stratify mortality risk among hospitalised Malawian children with severe pneumonia lacking recognised high-risk conditions.

Cardiovascular Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Cardiovascular dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE: We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children. DATA SOURCES: Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION: Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non-English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded. DATA EXTRACTION: Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member. RESULTS: Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition. LIMITATIONS: All included studies were observational and many were retrospective. CONCLUSIONS: The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction.

Antibiotic treatment failure in children aged 1 to 59 months with World Health Organization-defined severe pneumonia in Malawi: A CPAP IMPACT trial secondary analysis.

BACKGROUND: Pneumonia is a leading cause of mortality in children <5 years globally. Early identification of hospitalized children with pneumonia who may fail antibiotics could improve outcomes. We conducted a secondary analysis from the Malawi CPAP IMPACT trial evaluating risk factors for antibiotic failure among children hospitalized with pneumonia. METHODS: Participants were 1-59 months old with World Health Organization-defined severe pneumonia and hypoxemia, severe malnutrition, and/or HIV exposure/infection. All participants received intravenous antibiotics per standard care. First-line antibiotics were benzylpenicillin and gentamicin for five days. Study staff assessed patients for first-line antibiotic failure daily between days 3-6. When identified, patients failing antibiotics were switched to second-line ceftriaxone. Analyses excluded children receiving ceftriaxone and/or deceased by hospital day two. We compared characteristics between patients with and without treatment failure and fit multivariable logistic regression models to evaluate associations between treatment failure and admission characteristics. RESULTS: From June 2015-March 2018, 644 children were enrolled and 538 analyzed. Antibiotic failure was identified in 251 (46.7%) participants, and 19/251 (7.6%) died. Treatment failure occurred more frequently with severe malnutrition (50.2% (126/251) vs 28.2% (81/287), p<0.001) and amongst those dwelling ≥10km from a health facility (22.3% (56/251) vs 15.3% (44/287), p = 0.026). Severe malnutrition occurred more frequently among children living ≥10km from a health facility than those living <10km (49.0% (49/100) vs 35.7% (275/428), p = 0.014). Children with severe malnutrition (adjusted odds ratio (aOR) 2.2 (95% CI 1.52, 3.24), p<0.001) and pre-hospital antibiotics ((aOR 1.47, 95% CI 1.01, 2.14), p = 0.043) had an elevated aOR for antibiotic treatment failure. CONCLUSION: Severe malnutrition and pre-hospital antibiotic use predicted antibiotic treatment failure in this high-risk severe pneumonia pediatric population in Malawi. Our findings suggest addressing complex sociomedical conditions like severe malnutrition and improving pneumonia etiology diagnostics will be key for better targeting interventions to improve childhood pneumonia outcomes.

Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.

Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. Exposure: SARS-CoV-2 detected via nucleic acid testing. Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED). Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. Exposures: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing. Main Outcomes and Measures: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death. Results: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%). Conclusions and Relevance: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.

Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary.

Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.