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In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%-4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9-14)]; respiratory [9 (95% CI 5-13)]; and gastrointestinal [9 (95% CI 6-11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231-280)]; infectious [214 (95% CI 193-234)]; and gastrointestinal [166 (95% CI 143-190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation., Competing Interests: JC-C speaker for Novamed and Tecnoquimicas; received financial travel support from BAGO to attend the Colombian Congress of Pediatrics; participated in an Advisory Board for ZambonColombia; acted as an investigator in phase 2 and 3 clinical trials of Merck Sharp and Dhome drugs (antibiotics and monoclonal antibodies) that do not interfere in the course of this study. JL stock options in MERCK and MODERNA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor “CFO” declared a past co-authorship with the authors “NK & MOW”. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Kortz, Mediratta, Smith, Nielsen, Agulnik, Gordon Rivera, Reeves, O’Brien, Lee, Abbas, Attebery, Bacha, Bhutta, Biewen, Camacho-Cruz, Coronado Muñoz, deAlmeida, Domeryo Owusu, Fonseca, Hooli, Wynkoop, Leimanis-Laurens, Nicholaus Mally, McCarthy, Mutekanga, Pineda, Remy, Sanders, Tabor, Teixeira Rodrigues, Yuee Wang, Kissoon, Takwoingi, Wiens and Bhutta.)

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research., Competing Interests: Declaration of interests AA reports funding from the National Institutes of Health National Cancer Institute (R37CA276215–01) outside of this Health Policy. BMM reports funding from Eurogol and the National Research Foundation; reports royalties from the Society of Critical Care Medicine as Senior Associate Editor of Pediatric Critical Care Medicine; receives support for travel and meetings from the European Cystic Fibrosis Society, Critical Care Society of Southern Africa, and the South Africa Thoracic Society, all outside of this Health Policy; and is the unpaid President for the World Federation of Pediatric Intensive and Critical Care Society and the Critical Care Society of Southern Africa. JHL reports funding from the National Research Medical Council of Singapore and the Thrasher Foundation in the USA, outside of this Health Policy. VMN is the President of the Society of Critical Care Medicine. The views expressed in this Health Policy do not necessarily reflect those of the institutions to which the authors are affiliated. All other authors declare no competing interests., (Copyright © 2024 Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality., Objective: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature., Data Sources and Search Strategy: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 days to 12 years) hospitalized in LMICs and publications in English, Spanish, or French. Publications with non-original data (e.g., comments, editorials, letters, notes, conference materials) will be excluded., Study Selection: We will include observational studies published since January 1, 2005, that meet all eligibility criteria and for which a full text can be located., Data Extraction: Data extraction will include information related to study characteristics, hospital characteristics, underlying population characteristics, patient population characteristics, and outcomes., Data Synthesis: We will extract and report data on study, hospital, and patient characteristics; outcomes; and risk of bias. We will report the causes of admission and mortality by region, country income level, and age. We will report or calculate the case fatality rate (CFR) for each diagnosis when data allow., Conclusions: By understanding the burden of pediatric critical illness in LMICs, we can advocate for resources and inform resource allocation and investment decisions to improve the management and outcomes of children with acute pediatric critical illness in LMICs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YHM declared a shared affiliation with one of the authors JL to the handling editor at the time of review., (Copyright © 2022 Kortz, Nielsen, Mediratta, Reeves, O'Brien, Lee, Attebery, Bhutta, Biewen, Coronado Munoz, deAlmeida, Fonseca, Hooli, Johnson, Kissoon, Leimanis-Laurens, McCarthy, Pineda, Remy, Sanders, Takwoingi, Wiens, Bhutta and The Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network on Behalf of the PALISI Global Health Subgroup.)

Background: The burden of pediatric critical illness and resource utilization by children with critical illness in resource limited settings (RLS) are largely unknown. Without specific data that captures key aspects of critical illness, disease presentation, and resource utilization for pediatric populations in RLS, development of a contextual framework for appropriate, evidence-based interventions to guide allocation of limited but available resources is challenging. We present this methods paper which describes our efforts to determine the prevalence, etiology, hospital outcomes, and resource utilization associated with pediatric acute, critical illness in RLS globally., Methods: We will conduct a prospective, observational, multicenter, multinational point prevalence study in sixty-one participating RLS hospitals from North, Central and South America, Africa, Middle East and South Asia with four sampling time points over a 12-month period. Children aged 29 days to 14 years evaluated for acute illness or injury in an emergency department) or directly admitted to an inpatient unit will be enrolled and followed for hospital outcomes and resource utilization for the first seven days of hospitalization. The primary outcome will be prevalence of acute critical illness, which Global PARITY has defined as death within 48 hours of presentation to the hospital, including ED mortality; or admission/transfer to an HDU or ICU; or transfer to another institution for a higher level-of-care; or receiving critical care-level interventions (vasopressor infusion, invasive mechanical ventilation, non-invasive mechanical ventilation) regardless of location in the hospital, among children presenting to the hospital. Secondary outcomes include etiology of critical illness, in-hospital mortality, cause of death, resource utilization, length of hospital stay, and change in neurocognitive status. Data will be managed via REDCap, aggregated, and analyzed across sites., Discussion: This study is expected to address the current gap in understanding of the burden, etiology, resource utilization and outcomes associated with pediatric acute and critical illness in RLS. These data are crucial to inform future research and clinical management decisions and to improve global pediatric hospital outcomes., Competing Interests: DH is the owner of Analytical Solutions Group, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abbas, Holloway, Caporal, López-Barón, Agulnik, Remy, Appiah, Attebery, Fink, Lee, Hooli, Kissoon, Miller, Murthy, Muttalib, Nielsen, Puerto-Torres, Rodrigues, Sakaan, Rodrigues, Tabor, von Saint Andre-von Arnim, Wiens, Blackwelder, He, Kortz and Bhutta.)

Pediatric sepsis remains a significant cause of childhood morbidity and mortality, disproportionately affecting resource-limited settings. As more patients survive, it is paramount that we improve our understanding of post-sepsis morbidity and its impact on functional outcomes. The functional status scale (FSS) is a pediatric validated outcome measure quantifying functional impairment, previously demonstrating decreased function following critical illnesses, including sepsis, in resource-rich settings. However, functional outcomes utilizing the FSS in pediatric sepsis survivors have never been studied in resource-limited settings or in non-critically ill septic children. In a Tanzanian cohort of pediatric sepsis patients, we aimed to evaluate morbidity associated with an acute septic episode using the FSS modified for resource-limited settings. This was a prospective cohort study at an urban referral hospital in Tanzania, including children with sepsis aged 28 days to 14 years old over a 12-month period. The FSS was adapted to the site's available resources. Functional status scale scores were obtained by interviewing guardians both at the time of presentation to determine the child's baseline and at 28-day follow-up. The primary outcome was "decline in functional status," as defined by a change in FSS score of at least 3. In this cohort, 4.3% of the 1,359 surviving children completing 28-day follow-up had a "decline in functional status." Conversely, 13.8% of guardians reported that their child was not yet back to their pre-illness state. Three-quarters of children reported as not fully recovered were not identified via the FSS as having a decline in functional status. In our cohort of pediatric sepsis patients, we identified a low rate of decline in functional status when using the FSS adapted for resource-limited settings. A higher proportion of children were subjectively identified as not being recovered to baseline. This suggests that the FSS has limitations in this population, despite being adapted for resource-limited settings. Next steps include developing and validating a further revised FSS to better capture patients identified as not recovered but missed by the current FSS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lau-Braunhut, Smith, Steurer, Murray, Sawe, Matthay, Reynolds and Kortz.)

Background: Over 40% of the global burden of sepsis occurs in children under 5 years of age, making pediatric sepsis the top cause of death for this age group. Prior studies have shown that outcomes in children with sepsis improve by minimizing the time between symptom onset and treatment. This is a challenge in resource-limited settings where access to definitive care is limited. Methods: A secondary analysis was performed on data from 1,803 patients (28 days-14 years old) who presented to the emergency department (ED) at Muhimbili National Hospital (MNH) from July 1, 2016 to June 30, 2017 with a suspected infection and ≥2 clinical systemic inflammatory response syndrome criteria. The objective of this study was to determine the relationship between delayed presentation to definitive care (>48 h between fever onset and presentation to the ED) and mortality, as well as the association between socioeconomic status (SES) and delayed presentation. Multivariable logistic regression models tested the two relationships of interest. We report both unadjusted and adjusted odds ratios and 95% confidence intervals. Results: During the study period, 11.3% ( n = 203) of children who presented to MNH with sepsis died inhospital. Delayed presentation was more common in non-survivors ( n = 90/151, 60%) compared to survivors ( n = 614/1,353, 45%) ( p ≤ 0.01). Children who had delayed presentation to definitive care, compared to those who did not, had an adjusted odds ratio for mortality of 1.85 (95% CI: 1.17-3.00). Conclusions: Delayed presentation was an independent risk factor for mortality in this cohort, emphasizing the importance of timely presentation to care for pediatric sepsis patients. Potential interventions include more efficient referral networks and emergency transportation systems to MNH. Additional clinics or hospitals with pediatric critical care may reduce pediatric sepsis mortality in Tanzania, as well as parental education programs for recognizing pediatric sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Smith, Sawe, Matthay, Murray, Reynolds and Kortz.)

Abstract: Most children with coronavirus disease 2019 (COVID-19) infection are asymptomatic or have mild disease. About 5% of infected children will develop severe or critical disease. Rapid identification and treatment are essential for children who are critically ill with signs and symptoms of respiratory failure, septic shock, and multisystem inflammatory syndrome in children. This article is intended for pediatricians, pediatric emergency physicians, and individuals involved in the emergency care of children. It reviews the current epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children, summarizes key aspects of clinical assessment including identification of high-risk patients and manifestations of severe disease, and provides an overview of COVID-19 management in the emergency department based on clinical severity., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While health providers consistently use malaria rapid diagnostic tests to rule out malaria, they often lack tools to guide treatment for those febrile patients who test negative. Without the tools to provide an alternative diagnosis, providers may prescribe unnecessary antibiotics or miss a more serious condition, potentially contributing to antibiotic resistance and/or poor patient outcomes., Methods: This study ascertained which diagnoses and treatments might be associated with poor outcomes in adults who test negative for malaria. Adult patients for rapid diagnostic test of malaria seen in mobile health clinics in Mulanje and Phalombe districts were followed for 14 days. Participants were interviewed on sociodemographic characteristics, health-seeking behaviour, diagnosis, treatment and access to care. Mobile clinic medical charts were reviewed. Two weeks (±2 days) following clinic visit, follow-up interviews were conducted to assess whether symptoms had resolved., Results: Initially, 115 adult patients were enrolled and 1 (0.88%) was lost to follow-up. Of the 114 adult patients remaining in the study, 55 (48%) were seen during the dry season and 59 (52%) during the wet season. Symptoms resolved in 90 (80%) patients at the 14-day follow-up visit (n=90) with the rest (n=24) reporting no change in symptoms. None of the patients in the study died or were referred for further care. Almost all patients received some type of medication during their clinic visit (98.2%). Antibiotics were given to 38.6% of patients, and virtually all patients received pain or fever relief (96.5%). However, no anti-malarials were prescribed., Conclusions: Mobile clinics provide important health care where access to care is limited. Although rapid tests have guided appropriate treatment, challenges remain when a patient's presenting complaint is less well defined. In rural areas of southern Malawi, simple diagnostics are needed to guide treatment decisions., (© 2020 The College of Medicine and the Medical Association of Malawi.)

Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 β [IL-1β], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1β, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1β compared with the other subgroups. IL-1β best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.

Introduction: With the ability to diagnose malaria with rapid diagnostic tests (mRDT), interest in improving diagnostics for non-malarial fevers has increased. Understanding how health providers diagnose and treat fevers is important for identifying additional tools to improve outcomes and reduce unnecessary antibiotic prescribing, particularly in areas where access to laboratory diagnostics is limited. This study aimed to understand rural health providers' practice patterns, both quantitatively and qualitatively, and influences on diagnostic and treatment decision-making., Methods: A mixed-methods study was conducted in Mulanje and Phalombe districts in southern Malawi. Retrospective data on diagnoses and treatments of febrile illness from seven mobile clinic logbooks were collected for a 2-month period in both the dry and wet seasons. Mobile health clinics visited remote villages in southern Malawi once every 7 days. Records from all patients with a recorded axillary temperature of 37.5ºC or higher or reported history of fever within 48 hours, and a negative mRDT, were included in the analysis. Key informant interviews were conducted with 31 mobile clinic health workers who triage, diagnose, and treat patients as well as dispense medication., Results: In total, 30 672 febrile patients were seen during the study period. Of those, 9924 (32%) tested negative for malaria by mRDT. Acute respiratory infection was the most common diagnosis for mRDT-negative patients (44.6%), and this number increased in the rainy season as compared to the dry season (odds ratio=2.18, 95% confidence interval=2.01-2.36). Over half (60%) of mRDT-negative patients received antibiotics as a treatment. Almost all the health providers in this study reported limited training in non-malarial fever management, despite the fact that roughly 30% of all patients with fever seen at the mobile clinics tested negative by mRDT. Without diagnostic tools beyond mRDTs, providers relied heavily on patient history to guide treatment decisions., Conclusion: Additional simple-to-use diagnostic tests as well as additional training in patient examination and clinical assessment are needed in rural settings where health providers risk over-prescribing antibiotics or missing a potentially dangerous infection in febrile patients who test negative for malaria.

Objective . To characterize children with non-malarial fever at risk of nonrecovery or worsening in rural Malawi. Methods . This is a subgroup analysis of patients ≤14 years of age from a prospective cohort study in non-malarial fever subjects (temperature ≥37.5°C, or fever within 48 hours, and malaria negative) in southern Malawi cared for at a mobile clinic during the 2016 dry (August to September) or wet (November to December) season. Data collection included chart review and questionnaires; 14-day follow-up was conducted. We conducted univariate descriptive statistics on cohort characteristics, bivariate analyses to examine associations between characteristics and outcomes, and multivariate logistic regressions to explore factors associated with nonrecovery. Results . A total of 2893 patients were screened, 401 were enrolled, 286 of these were children, and 280 children completed follow-up. Eighty-seven percent reported symptom resolution, 12.9% reported no improvement, and there were no deaths or hospitalizations. No improvement was associated with dry season presentation (42.6% vs 75.0%, P < .0003), >2 days of symptoms (51.6% vs 72.2%, P = .03), and food insecurity (62.3% vs 86.1%, P = .007). Dry season subjects had a 4.35 times greater likelihood of nonimprovement (95% confidence interval [CI] = 1.96-11.11). Household food insecurity and being >2 hours from a permanent clinic were associated with no improvement (adjusted odds ratio [AOR] = 4.61, 95% CI = 1.81-14.29; and AOR = 2.38, 95% CI = 1.11-5.36, respectively). Conclusion . Outcomes were generally excellent in this rural, outpatient pediatric cohort, though risk factors for nonrecovery included food insecurity, access to a standing clinic, and seasonality. Ideally, this study will inform clinic- and policy-level changes aimed at ameliorating the modifiable risk factors in Malawi and throughout rural Africa., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: There is need for more data on critical care outcomes and interventions from low- and middle-income countries (LMIC). Global research collaborations could help improve health-care delivery for critically ill children in LMIC where child mortality rates remain high., Materials and Methods: To inform the role of collaborative research in health-care delivery for critically ill children in LMIC, an anonymous online survey of pediatric critical care (PCC) physicians from LMIC was conducted to assess priorities, major challenges, and potential solutions to PCC research. A convenience sample of 56 clinician-researchers taking care of critically ill children in LMIC was targeted. In addition, the survey was made available on a Latin American PCC website. Descriptive statistics were used for data analysis., Results: The majority of the 47 survey respondents worked at urban, public teaching hospitals in LMIC. Respondents stated their primary PCC research motivations were to improve clinical care and establish guidelines to standardize care. Top challenges to conducting research were lack of funding, high clinical workload, and limited research support staff. Respondent-proposed solutions to these challenges included increasing research funding options for LMIC, better access to mentors from high-income countries, research training and networks, and higher quality medical record documentation., Conclusion: LMIC clinician-researchers must be better empowered and resourced to lead and influence the local and global health research agenda for critically ill children. Increased funding options, access to training and mentorship in research methodology, and improved data collection systems for LMIC PCC researchers were recognized as key needs for success.

Background: Pediatric sepsis causes significant global morbidity and mortality and low- and middle-income countries (LMICs) bear the bulk of the burden. International sepsis guidelines may not be relevant in LMICs, especially in sub-Saharan Africa (SSA), due to resource constraints and population differences. There is a critical lack of pediatric sepsis data from SSA, without which accurate risk stratification tools and context-appropriate, evidence-based protocols cannot be developed. The study's objectives were to characterize pediatric sepsis presentations, interventions, and outcomes in a public Emergency Medicine Department (EMD) in Tanzania., Methods: Prospective descriptive study of children (28 days to 14 years) with sepsis [suspected infection with ≥2 clinical systemic inflammatory response syndrome (SIRS) criteria] presenting to a tertiary EMD in Dar es Salaam, Tanzania (July 1 to September 30, 2016). Outcomes included: in-hospital mortality (primary), EMD mortality, and hospital length of stay. We report descriptive statistics using means and SDs, medians and interquartile ranges, and counts and percentages as appropriate. Predictive abilities of SIRS criteria, the Alert-Verbal-Painful-Unresponsive (AVPU) score and the Lambaréné Organ Dysfunction Score (LODS) for in-hospital, early and late mortality were tested., Results: Of the 2,232 children screened, 433 (19.4%) met inclusion criteria, and 405 were enrolled. There were 247 (61%) subjects referred from an outside facility. Approximately half (54.1%) received antibiotics in the EMD, and some form of microbiologic culture was collected in 35.8% ( n  = 145) of subjects. In-hospital and EMD mortality were 14.2 and 1.5%, respectively, median time to death was 3 days (IQR 1-6), and median length of stay was 6 days (IQR 1-12). SIRS criteria, the AVPU score, and the LODS had low positive (17-27.1, 33.3-43.9, 18.3-55.6%, respectively) and high negative predictive values (88.6-89.8, 86.5-91.2, 86.8-90.5%, respectively) for in-hospital mortality., Conclusion: This pediatric sepsis cohort had high and early in-hospital mortality. Current criteria and tested clinical scores were inadequate for risk-stratification and mortality prediction in this population and setting. Pediatric sepsis management must take into account the local patient population, etiologies of sepsis, healthcare system, and resource availability. Only through studies such as this that generate regional data in LMICs can accurate risk stratification tools and context-appropriate, evidence-based guidelines be developed.

Background: Pediatric sepsis has a high mortality rate in limited resource settings. Sepsis protocols have been shown to be a cost-effective strategy to improve morbidity and mortality in a variety of populations and settings. At Dhaka Hospital in Bangladesh, mortality from pediatric sepsis in high-risk children previously approached 60%, which prompted the implementation of an evidenced-based protocol in 2010. The clinical effectiveness of this protocol had not been measured. We hypothesized that implementation of a pediatric sepsis protocol improved clinical outcomes, including reducing mortality and length of hospital stay., Materials and Methods: This was a retrospective cohort study of children 1-59 months old with a diagnosis of sepsis, severe sepsis or septic shock admitted to Dhaka Hospital from 10/25/2009-10/25/2011. The primary outcome was inpatient mortality pre- and post-protocol implementation. Secondary outcomes included fluid overload, heart failure, respiratory insufficiency, length of hospital stay, and protocol compliance, as measured by antibiotic and fluid bolus administration within 60 minutes of hospital presentation., Results: 404 patients were identified by a key-word search of the electronic medical record; 328 patients with a primary diagnosis of sepsis, severe sepsis, or septic shock were included (143 pre- and185 post-protocol) in the analysis. Pre- and post-protocol mortality were similar and not statistically significant (32.17% vs. 34.59%, p = 0.72). The adjusted odds ratio (AOR) for post-protocol mortality was 1.55 (95% CI, 0.88-2.71). The odds for developing fluid overload were significantly higher post-protocol (AOR 3.45, 95% CI, 2.04-5.85), as were the odds of developing heart failure (AOR 4.52, 95% CI, 1.43-14.29) and having a longer median length of stay (AOR 1.81, 95% CI 1.10-2.96). There was no statistically significant difference in respiratory insufficiency (pre- 65.7% vs. post- 70.3%, p = 0.4) or antibiotic administration between the cohorts (pre- 16.08% vs. post- 12.43%, p = 0.42)., Conclusions: Implementation of a pediatric sepsis protocol did not improve all-cause mortality or length of stay and may have been associated with increased fluid overload and heart failure during the study period in a large, non-governmental hospital in Bangladesh. Similar rates of early antibiotic administration may indicate poor protocol compliance. Though evidenced-based protocols are a potential cost-effective strategy to improve outcomes, future studies should focus on optimal implementation of context-relevant sepsis protocols in limited resource settings.

Objectives: Pneumonia is the largest infectious cause of death in children under 5 years globally, and limited resource settings bear an overwhelming proportion of this disease burden. Bubble continuous positive airway pressure (bCPAP), an accepted supportive therapy, is often thought of as cost-prohibitive in these settings. We hypothesise that bCPAP is a cost-effective intervention in a limited resource setting and this study aims to determine the cost-effectiveness of bCPAP, using Malawi as an example., Design: Cost-effectiveness analysis., Setting: District and central hospitals in Malawi., Participants: Children aged 1 month-5 years with severe pneumonia, as defined by WHO criteria., Interventions: Using a decision tree analysis, we compared standard of care (including low-flow oxygen and antibiotics) to standard of care plus bCPAP., Primary and Secondary Outcome Measures: For each treatment arm, we determined the costs, clinical outcomes and averted disability-adjusted life years (DALYs). We assigned input values from a review of the literature, including applicable clinical trials, and calculated an incremental cost-effectiveness ratio (ICER)., Results: In the base case analysis, the cost of bCPAP per patient was $15 per day and $41 per hospitalisation, with an incremental net cost of $64 per pneumonia episode. bCPAP averts 5.0 DALYs per child treated, with an ICER of $12.88 per DALY averted compared with standard of care. In one-way sensitivity analyses, the most influential uncertainties were case fatality rates (ICER range $9-32 per DALY averted). In a multi-way sensitivity analysis, the median ICER was $12.97 per DALY averted (90% CI, $12.77 to $12.99)., Conclusion: bCPAP is a cost-effective intervention for severe paediatric pneumonia in Malawi. These results may be used to inform policy decisions, including support for widespread use of bCPAP in similar settings., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)