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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., (© 2024 Society for Academic Emergency Medicine.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

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., Competing Interests: Declaration of Competing Interest The authors have no disclosures or financial conflicts of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 × 10 9 /L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 10 9 /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., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Mvalo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: Dr. Mkaliainga received funding from the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine. Dr. Banda’s institution received funding from a divisional small grant from Cincinnati Children’s Hospital Medical Center. Dr. Byczkowski disclosed that she taught a fellow class on statistical process control at Seattle Children’s Hospital. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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.

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, χ 2 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

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.

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., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

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., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

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., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Introduction: Pneumonia is a frequent and costly cause of emergency department (ED) visits and hospitalisations in children. There are no evidence-based, validated tools to assist physicians in management and disposition decisions for children presenting to the ED with community-acquired pneumonia (CAP). The objective of this study is to develop a clinical prediction model to accurately stratify children with CAP who are at risk for low, moderate and severe disease across a global network of EDs., Methods and Analysis: This study is a prospective cohort study enrolling up to 4700 children with CAP at EDs at ~80 member sites of the Pediatric Emergency Research Networks (PERN; https://pern-global.com/). We will include children aged 3 months to <14 years with a clinical diagnosis of CAP. We will exclude children with hospital admissions within 7 days prior to the study visit, hospital-acquired pneumonias or chronic complex conditions. Clinical, laboratory and imaging data from the ED visit and hospitalisations within 7 days will be collected. A follow-up telephone or text survey will be completed 7-14 days after the visit. The primary outcome is a three-tier composite of disease severity. Ordinal logistic regression, assuming a partial proportional odds specification, and recursive partitioning will be used to develop the risk stratification models., Ethics and Dissemination: This study will result in a clinical prediction model to accurately identify risk of severe disease on presentation to the ED. Ethics approval was obtained for all sites included in the study. Cincinnati Children's Hospital Institutional Review Board (IRB) serves as the central IRB for most US sites. Informed consent will be obtained from all participants. Results will be disseminated through international conferences and peer-reviewed publications. This study overcomes limitations of prior pneumonia severity scores by allowing for broad generalisability of findings, which can be actively implemented after model development and validation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

As the field of global child health increasingly focuses on inpatient and emergency care, there is broad recognition of the need for comprehensive, accurate data to guide decision-making at both patient and system levels. Limited financial and human resources present barriers to reliable and detailed clinical documentation at hospitals in low-and-middle-income countries (LMICs). Kamuzu Central Hospital (KCH) is a tertiary referral hospital in Malawi where the paediatric ward admits up to 3000 children per month. To improve availability of robust inpatient data, we collaboratively designed an acute care database on behalf of PACHIMAKE, a consortium of Malawi and US-based institutions formed to improve paediatric care at KCH. We assessed the existing health information systems at KCH, reviewed quality care metrics, engaged clinical providers and interviewed local stakeholders who would directly use the database or be involved in its collection. Based on the information gathered, we developed electronic forms collecting data at admission, follow-up and discharge for children admitted to the KCH paediatric wards. The forms record demographic information, basic medical history, clinical condition and pre-referral management; track diagnostic processes, including laboratory studies, imaging modalities and consults; and document the final diagnoses and disposition obtained from clinical files and corroborated through review of existing admission and death registries. Our experience with the creation of this database underscores the importance of fully assessing existing health information systems and involving all stakeholders early in the planning process to ensure meaningful and sustainable implementation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the acceptability of bubble continuous positive airway pressure (bCPAP) and low-flow oxygen among mothers of children who had received either therapy., Setting: A district hospital in Salima, Malawi., Participants: We conducted eight focus group discussions (FGDs) with a total of 54 participants. Eligible participants were mothers of children 1 to 59 months of age with severe pneumonia and a comorbidity (HIV-infection, HIV-exposure, malnutrition or hypoxaemia) who, with informed consent, had been enrolled in a randomised clinical trial, CPAP IMPACT (Improving Mortality for Pneumonia in African Children Trial), comparing low-flow oxygen and bCPAP treatments (ClinicalTrials.gov, NCT02484183)., Primary and Secondary Outcome Measures: FGDs assessed mothers' attitudes and feelings towards oxygen and bCPAP before and after therapy along with general community perceptions of respiratory therapies. Data was analysed using inductive thematic analysis to assess themes and subthemes of the transcripts., Results: Community perceptions of oxygen and bCPAP were widely negative. Mothers recounted that they are told that 'oxygen kills babies'. They are often fearful of allowing their child to receive oxygen therapy and will delay treatment or seek alternative therapies. Mothers report limiting oxygen and bCPAP by intermittently removing the nasal cannulas or mask. After oxygen or bCPAP treatment, regardless of patient outcome, mothers were supportive of the treatment their child received and would recommend it to other mothers., Conclusion: There are significant community misconceptions around oxygen and bCPAP causing mothers to be fearful of either treatment. In order for low-flow oxygen treatment and bCPAP implementation to be effective, widespread community education is necessary., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background and Objectives: Antibiotic therapy is often prescribed for suspected community-acquired pneumonia (CAP) in children despite a lack of knowledge of causative pathogen. Our objective in this study was to investigate the association between antibiotic prescription and treatment failure in children with suspected CAP who are discharged from the hospital emergency department (ED)., Methods: We performed a prospective cohort study of children (ages 3 months-18 years) who were discharged from the ED with suspected CAP. The primary exposure was antibiotic receipt or prescription. The primary outcome was treatment failure (ie, hospitalization after being discharged from the ED, return visit with antibiotic initiation or change, or antibiotic change within 7-15 days from the ED visit). The secondary outcomes included parent-reported quality-of-life measures. Propensity score matching was used to limit potential bias attributable to treatment selection between children who did and did not receive an antibiotic prescription., Results: Of 337 eligible children, 294 were matched on the basis of propensity score. There was no statistical difference in treatment failure between children who received antibiotics and those who did not (odds ratio 1.0; 95% confidence interval 0.45-2.2). There was no difference in the proportion of children with return visits with hospitalization (3.4% with antibiotics versus 3.4% without), initiation and/or change of antibiotics (4.8% vs 6.1%), or parent-reported quality-of-life measures., Conclusions: Among children with suspected CAP, the outcomes were not statistically different between those who did and did not receive an antibiotic prescription., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background : There are scarce data on outcomes of in-hospital paediatric cardiac arrest (CA) in resource-poor settings and none for World Bank-defined low-income countries. Aim : To report the outcomes of in-hospital paediatric CA from a university-affiliated referral hospital in Malawi. Methods : Data were collected prospectively on patients aged 30 days to 13 years who experienced CA and underwent cardiopulmonary resuscitation (CPR) at Kamuzu Central Hospital in Lilongwe, Malawi from January through June 2017. Utstein-style reporting guidelines for CAs were used to define outcomes; the primary outcome was survival to hospital discharge. A data collection form was used to record patient, arrest and resuscitation characteristics. Results : A total of 135 patients fulfilled the criteria for inclusion in the study. Resuscitation outcomes are presented in Figure 1 using a modified Utstein template. In-hospital CA was associated with 100% mortality. Return of spontaneous circulation (ROSC) was obtained in 6% of patients and sustained ROSC in 4%; 24-h survival was zero. The most common admission diagnosis was malaria (51%). Most arrests occurred on the paediatric ward (90%) rather than critical care units. Most resuscitations were led by trainees and mid-level providers (58%) rather than paediatricians (23%). Conclusion : Survival following in-hospital paediatric CA was zero, suggesting that CPR may have no benefit in this tertiary hospital. Future efforts to improve outcomes should focus on advocating better pre-arrest care and research interventions aimed to identify and treat children at risk of CA within the resource constraints of this setting.

Background: Pneumonia is the leading cause of death among children globally. Most pneumonia deaths in low-income and middle-income countries (LMICs) occur among children with HIV infection or exposure, severe malnutrition, or hypoxaemia despite antibiotics and oxygen. Non-invasive bubble continuous positive airway pressure (bCPAP) is considered a safe ventilation modality that might improve child pneumonia survival. bCPAP outcomes for high-risk African children with severe pneumonia are unknown. Since most child pneumonia hospitalisations in Africa occur in non-tertiary district hospitals without daily physician oversight, we aimed to examine whether bCPAP improves severe pneumonia mortality in such settings., Methods: This open-label, randomised, controlled trial was done in the general paediatric ward of Salima District Hospital, Malawi. We enrolled children aged 1-59 months old with WHO-defined severe pneumonia and either HIV infection or exposure, severe malnutrition, or an oxygen saturation of less than 90%. Children were randomly assigned 1:1 to low-flow nasal cannula oxygen or nasal bCPAP. Non-physicians administered care; the primary outcome was hospital survival. Primary analyses were by intention-to-treat and interim and adverse events analyses per protocol. This trial is registered with ClinicalTrials.gov, number NCT02484183, and is closed., Findings: We screened 1712 children for eligibility between June 23, 2015, and March 21, 2018. The data safety and monitoring board stopped the trial for futility after 644 of the intended 900 participants were enrolled. 323 children were randomly assigned to oxygen and 321 to bCPAP. 35 (11%) of 323 children who received oxygen died in hospital, as did 53 (17%) of 321 who received bCPAP (relative risk 1·52; 95% CI 1·02-2·27; p=0·036). 13 oxygen and 17 bCPAP patients lacked hospital outcomes and were considered lost to follow-up. Suspected adverse events related to treatment occurred in 11 (3%) of 321 children receiving bCPAP and 1 (<1%) of 323 children receiving oxygen. Four bCPAP and one oxygen group deaths were classified as probable aspiration episodes, one bCPAP death as probable pneumothorax, and six non-death bCPAP events included skin breakdown around the nares., Interpretation: bCPAP treatment in a paediatric ward without daily physician supervision did not reduce hospital mortality among high-risk Malawian children with severe pneumonia, compared with oxygen. The use of bCPAP within certain patient populations and non-intensive care settings might carry risk that was not previously recognised. bCPAP in LMICs needs further evaluation before wider implementation for child pneumonia care., Funding: Bill & Melinda Gates Foundation, International AIDS Society, Health Empowering Humanity., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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.

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.

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.

We report on a high-power passively mode-locked radially polarized Yb:YAG thin-disk oscillator providing 125 W of average output power. To the best of our knowledge, this is the highest average power ever reported from a mode-locked radially polarized oscillator without subsequent amplification stages. Mode-locking was achieved by implementing a SESAM as the cavity end mirror and the radial polarization of the LG* 01 mode was obtained by means of a circular Grating Waveguide Output Coupler. The repetition rate was 78 MHz. A pulse duration of 0.97 ps and a spectral bandwidth of 1.4 nm (FWHM) were measured at the maximum output power. This corresponds to a pulse energy of 1.6 µJ and a pulse peak power of 1.45 MW. A high degree of radial polarization of 97.3 ± 1% and an M 2 -value of 2.16 which is close to the theoretical value for the LG* 01 doughnut mode were measured.

The objective of this review is to explain the science of metabolomics-a science of systems biology that measures and studies endogenous small molecules (metabolites) that are present in a single biological sample-and its application to the diagnosis and treatment of sepsis. In addition, we discuss how discovery through metabolomics can contribute to the development of precision medicine targets for this complex disease state and the potential avenues for those new discoveries to be applied in the clinical environment. A nonsystematic literature review was performed focusing on metabolomics, pharmacometabolomics, and sepsis. Human (adult and pediatric) and animal studies were included. Metabolomics has been investigated in the diagnosis, prognosis, and risk stratification of sepsis, as well as for the identification of drug target opportunities. Metabolomics elucidates a new level of detail when compared with other systems biology sciences, with regard to the metabolites that are most relevant in the pathophysiology of sepsis, as well as highlighting specific biochemical pathways at work in sepsis. Metabolomics also highlights biochemical differences between sepsis survivors and nonsurvivors at a level of detail greater than that demonstrated by genomics, transcriptomics, or proteomics, potentially leading to actionable targets for new therapies. The application of pharmacometabolomics and its integration with other systems pharmacology to sepsis therapeutics could be particularly helpful in differentiating drug responders and nonresponders and furthering knowledge of mechanisms of drug action and response. The accumulated literature on metabolomics suggests it is a viable tool for continued discovery around the pathophysiology, diagnosis and prognosis, and treatment of sepsis in both adults and children, and it provides a greater level of biochemical detail and insight than other systems biology approaches. However, the clinical application of metabolomics in sepsis has not yet been fully realized. Prospective validation studies are needed to translate metabolites from the discovery phase into the clinical utility phase., (© 2017 Pharmacotherapy Publications, Inc.)

Introduction: To achieve sustained reductions in child mortality in low- and middle-income countries, increased local capacity is necessary. One approach to capacity building is support offered via partnerships with institutions in high-income countries. However, lack of cooperation between institutions can create barriers to successful implementation of programs and may inadvertently weaken the health system they are striving to improve. A coordinated approach is necessary., Background: Three U.S.-based institutions have separately supported various aspects of pediatric care at Kamuzu Central Hospital (KCH), the main government referral hospital in the central region of Malawi, for several years. Within each institution's experience, common themes were recognized, which required attention in order to sustain improvements in care. Each recognized that support of clinical care is a necessary cornerstone before initiating educational or training efforts. In particular, the support of emergency and acute care is paramount in order to decrease in-hospital mortality. Through the combined efforts of Malawian partners and the US-based institutions, the pediatric mortality rate has decreased from >10 to <4% since 2011, yet critical gaps remain. To achieve further improvements, representatives with expertise in pediatric emergency medicine (PEM) from each US-based institution hypothesized that coordinated efforts would be most effective, decrease duplication, improve communication, and ensure that investments in education and training are aligned with local priorities., Call to Action: Together with local stakeholders, the three US-based partners created a multi-institutional partnership, Pediatric Alliance for Child Health Improvement in Malawi at Kamuzu Central Hospital and Environs (PACHIMAKE). Representatives from each institution gathered in Malawi late 2016 and sought input and support from local partners at all levels to prioritize interventions, which could be collectively undertaken by this consortium. Long- and short-term goals were identified and approved by local partners and will be implemented through a phased approach., Conclusion: The development of a novel partnership between relevant stakeholders in Malawi and US-based partners with expertise in PEM should help to further decrease pediatric mortality through the coordinated provision of acute care expertise and training as well as investment in the development of educational, research, and clinical efforts in PEM at KCH.

Introduction: Pneumonia is a leading cause of mortality among children in low-resource settings. Mortality is greatest among children with high-risk conditions including HIV infection or exposure, severe malnutrition and/or severe hypoxaemia. WHO treatment recommendations include low-flow oxygen for children with severe pneumonia. Bubble continuous positive airway pressure (bCPAP) is a non-invasive support modality that provides positive end-expiratory pressure and oxygen. bCPAP is effective in the treatment of neonates in low-resource settings; its efficacy is unknown for high-risk children with severe pneumonia in low-resource settings., Methods and Analysis: CPAP IMPACT is a randomised clinical trial comparing bCPAP to low-flow oxygen in the treatment of severe pneumonia among high-risk children 1-59 months of age. High-risk children are stratified into two subgroups: (1) HIV infection or exposure and/or severe malnutrition; (2) severe hypoxaemia. The trial is being conducted in a Malawi district hospital and will enrol 900 participants. The primary outcome is in-hospital mortality rate of children treated with standard care as compared with bCPAP., Ethics and Dissemination: CPAP IMPACT has approval from the Institutional Review Boards of all investigators. An urgent need exists to determine whether bCPAP decreases mortality among high-risk children with severe pneumonia to inform resource utilisation in low-resource settings., Trial Registration Number: NCT02484183; Pre-results., Competing Interests: Competing interests: None declared.

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.

We report on the first demonstration of a radially polarized passively mode-locked thin-disk oscillator. Radial polarization was achieved by the use of a novel circular grating waveguide output coupler. We showed mode-locked operation up to a maximum average output power of 13.3 W with an optical efficiency of 21.8%. The degree of radial polarization of the emitted beam was measured to be 97±1%. The laser system generated pulses with a duration of 907 fs and an energy of 316 nJ corresponding to a peak power of 0.35 MW. To the best of our knowledge, these values exceed the performance of previously reported radially polarized mode-locked oscillator systems.

We demonstrate a three-stage diode-pumped Yb:YAG single-crystal-fiber amplifier to generate femtosecond pulses at high average powers with linear or cylindrical (i.e., radial or azimuthal) polarization. At a repetition rate of 20 MHz, 750-fs pulses were obtained at an average power of 85 W in cylindrical polarization and at 100 W in linear polarization. The report includes investigations on the use of Yb:YAG single-crystal fibers with different length/doping ratio and the zero-phonon pumping at a wavelength of 969 nm in order to optimize the performance.

A diode-pumped actively Q-switched and actively mode-locked Tm3+-doped double-clad silicate fiber laser is reported providing up to 5 W of average output power at ~60 kHz Q-switch envelope repetition rate and ~8 μJ subpulses with up to 2.4 kW peak power. Using this source as a pump laser for supercontinuum generation in a ZBLAN fiber, over 1080 mW of supercontinuum from 1.9 μm to beyond 3.6 μm was obtained at an overall efficiency of 3.3% with respect to the diode pump power.

Human memory cells acquire resistance to several types of suppressor cells, including MLR generated suppressor cells. These data suggest one possible mechanism of that resistance, namely retention of IL-2 receptors in the resting state. Cells from a 7-day MLR were separated on a single step percoll gradient. All proliferating cells were found in the interface. Pellet cells were nondividing. Interface and pellet cells had equivalent memory function in a secondary MLR. Thus, there appear to be at least two subpopulations of memory cells, including one that is primed without undergoing division. These subpopulations are functionally distinct. Interface memory cells were 30-50% more resistant than pellet memory cells to MLR generated suppressor cells. On culture day 10, neither pellet nor interface cells displayed significant spontaneous proliferation but exogenous Interleukin 2 (IL-2) produced up to five times as much proliferation in interface cells as in pellet cells. Further, FACS analysis with an anti-TAC equivalent antibody also showed that significantly more interface cells have surface receptors for IL-2. Thus, cells that had previously divided continue to have more and/or higher affinity receptors for IL-2 even after return to the resting state. If a mechanism of suppression in the mixed lymphocyte reaction is to reduce the synthesis/release of Il-2, memory cells may acquire their relative resistance to this suppression by virtue of the increased IL-2 sensitivity of this discrete subpopulation.