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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Blood transfusion and mortality in children with severe anaemia in a malaria-endemic region.

BACKGROUND: In children in sub-Saharan Africa, severe anaemia (SA) is an important cause of mortality, and malaria is a primary cause. The World Health Organization (WHO) recommends blood transfusion for all children with haemoglobin (Hb) <4 g/dL and for those with Hb 4-6 g/dL with signs of instability. In sub-Saharan Africa, evidence of the effect on mortality of transfusion in children with SA with and without malaria is mixed. AIM: To determine in children with and without malaria whether receipt of transfusion was associated with lower mortality at WHO transfusion thresholds. METHODS: This was a retrospective cohort study of 1761 children with SA (Hb ≤6 g/dL) admitted to Kamuzu Central Hospital in Malawi. In those whose Hb was 4-6 g/dL, mortality was compared by transfusion, stratified by haemoglobin, malaria status and signs of instability. RESULTS: Children with profound anaemia (Hb <4 g/dL) and malaria were the only subgroup who had a significant decrease in the odds of in-hospital death if they received a transfusion (OR 0.43, p = 0.01). Although children with Hb 4-6 g/dL and at least one sign of instability had higher mortality than children with none, there was no difference in the odds of mortality between those who received a transfusion and those who did not (OR 1.16, p = 0.62). CONCLUSIONS: This study suggests that transfusion of children with profound anaemia and malaria may confer increased in-hospital survival. An understanding of the factors associated with mortality from SA will allow for interventions to prioritise the provision of limited blood.

High-Flow Nasal Cannula in Bronchiolitis at a Pediatric Emergency Department: Trends and Outcomes.

OBJECTIVES: Use of high-flow nasal cannula (HFNC) for bronchiolitis has increased, but data describing the current use and impact of this therapy are limited. Our objective with this study was to describe the use of HFNC for bronchiolitis in a pediatric emergency department (ED) from 2013 to 2019 and to explore associations with clinical outcomes. METHODS: This was a retrospective cohort study of children aged 2 to 24 months with the diagnosis of bronchiolitis. The primary outcome was HFNC initiation in the ED. Secondary outcomes included admission rate, ICU (PICU) admission, transfer to PICU from floor, and endotracheal intubation. An adjusted interrupted times series analysis was performed to analyze changes in rates of primary and secondary outcomes over time. RESULTS: In total 11 149 children met inclusion criteria; 902 (8.1%) were initiated on HFNC. The rate of HFNC initiation increased from 1.3% in 2012-2013 to 17.0% in 2018-2019 (P trend ≤ .001). Less than 30% of children initiated on HFNC were hypoxic. There were no significant changes over time in rates of hospital admission, PICU admission, or PICU transfer, adjusting for clinical severity, seasonality, and provider variation. Intubation rate increased over the study period. CONCLUSIONS: We found a 13-fold increase in HFNC use over a 6-year period with no evidence of improvement in clinically meaningful outcomes. Clinical benefit should be clearly defined before further expansion of the use of HFNC for bronchiolitis in the ED.

Relationship between distance of referring facilities and haemoglobin change in children in Malawi.

BACKGROUND: Anaemia is a significant cause of mortality in children in sub-Saharan Africa where blood transfusion is often available only at referral hospitals. Understanding the pattern of referrals by health facilities is essential to identify the delays that affect child survival. AIM: To determine if there was a correlation between change in haemoglobin (Hb) level and distance from referring facilities to Kamuzu Central Hospital (KCH) in Malawi, and whether distance affected mortality rates. METHODS: This was a retrospective cohort study of 2259 children referred to KCH whose Hb was measured at the referring facility or at KCH. Maps were created using ArcGIS® software. The relationship between distance from KCH and change in Hb was assessed by χ2 analysis and multiple linear regression with SAS© software. RESULTS: The majority of children were referred by health facilities in the Lilongwe District. When categorised as Hb <4, 4-6 or >6 g/dL, 87.0% of children remained in the same category during transfer. There was no significant relationship between Hb drop and distance from KCH. Distance from KCH was not a significant predictor of Hb level at KCH or Hb change. However, mortality rates were significantly higher in facilities that were 10-50 km from KCH than in those which were <10 km away. CONCLUSIONS: Using distance as a proxy for time, this suggests that referring facilities are transferring children sufficiently quickly to avert significant reductions in Hb. Despite this, there is a need to identify the factors that influence the decision to transfer anaemic children.