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Background: More than 50 countries, mainly in Sub-Saharan Africa and South Asia, are not on course to meet the neonatal and under-five mortality target set by the Sustainable Development Goals (SDGs) for the year 2030. One important, yet neglected, aspect of child mortality rates is deaths occurring during the post-discharge period. For children living in resource-poor countries, the rate of post-discharge mortality within the first several months after discharge is often as high as the rates observed during the initial admission period. This has generally been observed within the context of acute illness and has been closely linked to underlying conditions such as malnutrition, HIV, and anemia. These post-discharge mortality rates tend to be underreported and present a major oversight in the efforts to reduce overall child mortality. This review will explore recurrent illness following discharge through determination of rates of, and risk factors for, pediatric post-discharge mortality in resource-poor settings., Methods: Eligible studies will be retrieved using MEDLINE, EMBASE, and CINAHL databases. Only studies with a post-discharge observation period of more than 7 days following discharge will be eligible for inclusion. Secondary outcomes will include post-discharge mortality relative to in-hospital mortality, overall readmission rates, pooled estimates of risk factors (e.g. admission details vs discharge factors, clinical vs social factors), pooled post-discharge mortality Kaplan-Meier survival curves, and outcomes by disease subgroups (e.g. malnutrition, anemia, general admissions). A narrative description of the included studies will be synthesized to categorize commonly affected patient population categories and a random-effects meta-analysis will be conducted to quantify overall post-discharge mortality rates at the 6-month time point., Discussion: Post-discharge mortality contributes to global child mortality rates with a greater burden of deaths occurring in resource-poor settings. Literature concentrated on child mortality published over the last decade has expanded to focus on the fatal outcomes of children post-discharge and associated risk factors. The results from this systematic review will inform current policy and interventions on the epidemiological burden of post-discharge mortality and morbidity following acute illness among children living in resource-poor settings., Systematic Review Registration: PROSPERO Registration ID: CRD42022350975., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chaudhry 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.)

Background: Neonatal multiparameter continuous physiological monitoring (MCPM) technologies assist with early detection of preventable and treatable causes of neonatal mortality. Evaluating accuracy of novel MCPM technologies is critical for their appropriate use and adoption., Methods: We prospectively compared the accuracy of Sibel's Advanced Neonatal Epidermal (ANNE) technology with Masimo's Rad-97 pulse CO-oximeter with capnography and Spengler's Tempo Easy reference technologies during four evaluation rounds. We compared accuracy of heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2), and skin temperature using Bland-Altman plots and root-mean-square deviation analyses (RMSD). Sibel's ANNE algorithms were optimized between each round. We created Clarke error grids with zones of 20% to aid with clinical interpretation of HR and RR results., Results: Between November 2019 and August 2020 we collected 320 hours of data from 84 neonates. In the final round, Sibel's ANNE technology demonstrated a normalized bias of 0% for HR and 3.1% for RR, and a non-normalized bias of -0.3% for SpO2 and 0.2°C for temperature. The normalized spread between 95% upper and lower limits-of-agreement (LOA) was 4.7% for HR and 29.3% for RR. RMSD for SpO2 was 1.9% and 1.5°C for temperature. Agreement between Sibel's ANNE technology and the reference technologies met the a priori-defined thresholds for 95% spread of LOA and RMSD. Clarke error grids showed that all HR and RR observations were within a 20% difference., Conclusion: Our findings suggest acceptable agreement between Sibel's ANNE and reference technologies. Clinical effectiveness, feasibility, usability, acceptability, and cost-effectiveness investigations are necessary for large-scale implementation., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Shuai Xu is Founder and Chief Executive Officer at Sibel Health; all other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Sepsis is a clinical syndrome characterized by organ dysfunction due to presumed or proven infection. Severe cases can have case fatality ratio 25% or higher in low-middle income countries, but early diagnosis and timely treatment have a proven benefit. The Smart Triage program in Jinja Regional Referral Hospital in Uganda will provide expedited sepsis treatment in children through a data-driven electronic patient triage system. To complement the ongoing Smart Triage interventional trial, we propose methods for a concurrent cost-effectiveness analysis of the Smart Triage platform., Methods: We will use a decision-analytic model taking a societal perspective, combining government and out-of-pocket costs, as patients bear a sizeable portion of healthcare costs in Uganda due to the lack of universal health coverage. Previously published secondary data will be used to link healthcare utilization with costs and intermediate outcomes with mortality. We will model uncertainty via probabilistic sensitivity analysis and present findings at various willingness-to-pay thresholds using a cost-effectiveness acceptability curve., Discussion: Our proposed analysis represents a first step in evaluating the cost-effectiveness of an innovative digital triage platform designed to improve clinical outcomes in pediatric sepsis through expediting care in low-resource settings. Our use of a decision analytic model to link secondary costing data, incorporate post-discharge healthcare utilization, and model clinical endpoints is also novel in the pediatric sepsis triage literature for low-middle income countries. Our analysis, together with subsequent analyses modelling budget impact and scale up, will inform future modifications to the Smart Triage platform, as well as motivate scale-up to the district and national levels., Trial Registration: Trial registration of parent clinical trial: NCT04304235, https://clinicaltrials.gov/ct2/show/NCT04304235. Registered 11 March 2020., Competing Interests: The authors have declared that no competing interests exist.

Background: Sepsis is the leading cause of death in children under five in low- and middle-income countries. The rapid identification of the sickest children and timely antibiotic administration may improve outcomes. We developed and implemented a digital triage platform to rapidly identify critically ill children to facilitate timely intravenous antibiotic administration., Objective: This quality improvement initiative sought to reduce the time to antibiotic administration at a dedicated children's hospital outpatient department in Mbarara, Uganda., Intervention and Study Design: The digital platform consisted of a mobile application that collects clinical signs, symptoms, and vital signs to prioritize children through a combination of emergency triggers and predictive risk algorithms. A computer-based dashboard enabled the prioritization of children by displaying an overview of all children and their triage categories. We evaluated the impact of the digital triage platform over an 11-week pre-implementation phase and an 11-week post-implementation phase. The time from the end of triage to antibiotic administration was compared to evaluate the quality improvement initiative., Results: There was a difference of -11 minutes (95% CI, -16.0 to -6.0; p < 0.001; Mann-Whitney U test) in time to antibiotics, from 51 minutes (IQR, 27.0-94.0) pre-implementation to 44 minutes (IQR, 19.0-74.0) post-implementation. Children prioritized as emergency received the greatest time benefit (-34 minutes; 95% CI, -9.0 to -58.0; p < 0.001; Mann-Whitney U test). The proportion of children who waited more than an hour until antibiotics decreased by 21.4% (p = 0.007)., Conclusion: A data-driven patient prioritization and continuous feedback for healthcare workers enabled by a digital triage platform led to expedited antibiotic therapy for critically ill children with sepsis. This platform may have a more significant impact in facilities without existing triage processes and prioritization of treatments, as is commonly encountered in low resource settings., Competing Interests: The authors have declared that no competing interests exist.

Sepsis is a life-threatening dysfunction of the immune system leading to multiorgan failure that is precipitated by infectious diseases and is a leading cause of death in children under 5 years of age. It is necessary to be able to identify a sick child at risk of developing sepsis at the earliest point of presentation to a healthcare facility so that appropriate care can be provided as soon as possible. Our study objective was to generate a list of consensus-driven predictor variables for the derivation of a prediction model that will be incorporated into a mobile device and operated by low-skilled healthcare workers at triage. By conducting a systematic literature review and examination of global guideline documents, a list of 72 initial candidate predictor variables was generated. A two-round modified Delphi process involving 26 experts from both resource-rich and resource-limited settings, who were also encouraged to suggest new variables, yielded a final list of 45 predictor variables after evaluating each variable based on three domains: predictive potential, measurement reliability, and level of training and resources required. The final list of predictor variables will be used to collect data and contribute to the derivation of a prediction model., Competing Interests: The authors have declared that no competing interests exist.

Background: Pediatric hospital mortality from infectious diseases in resource constrained countries remains unacceptably high. Improved methods of risk-stratification can assist in referral decision making and resource allocation. The purpose of this study was to create prediction models for in-hospital mortality among children admitted with suspected infectious diseases., Methods: This two-site prospective observational study enrolled children between 6 months and 5 years admitted with a proven or suspected infection. Baseline clinical and laboratory variables were collected on enrolled children. The primary outcome was death during admission. Stepwise logistic regression minimizing Akaike's information criterion was used to identify the most promising multivariate models. The final model was chosen based on parsimony., Results: 1307 children were enrolled consecutively, and 65 (5%) of whom died during their admission. Malaria, pneumonia and gastroenteritis were diagnosed in 50%, 31% and 8% of children, respectively. The primary model included an abnormal Blantyre coma scale, HIV and weight-for-age z-score. This model had an area under the curve (AUC) of 0.85 (95% CI, 0.80-0.89) with a sensitivity and specificity of 83% and 76%, respectively. The positive and negative predictive values were 15% and 99%, respectively. Two alternate models with similar performance characteristics were developed withholding HIV and weight-for-age z-score, for use when these variables are not available., Conclusions: Risk stratification of children admitted with infectious diseases can be calculated based on several easily measured variables. Risk stratification at admission can be used for allocation of scarce human and physical resources and to guide referral among children admitted to lower level health facilities.

Background: The reduction in the deaths of millions of children who die from infectious diseases requires early initiation of treatment and improved access to care available in health facilities. A major challenge is the lack of objective evidence to guide front line health workers in the community to recognize critical illness in children earlier in their course., Methods: We undertook a prospective observational study of children less than 5 years of age presenting at the outpatient or emergency department of a rural tertiary care hospital between October 2012 and April 2013. Study physicians collected clinical signs and symptoms from the facility records, and with a mobile application performed recordings of oxygen saturation, heart rate and respiratory rate. Facility physicians decided the need for hospital admission without knowledge of the oxygen saturation. Multiple logistic predictive models were tested., Findings: Twenty-five percent of the 3374 assessed children, with a median (interquartile range) age of 1.02 (0.42-2.24), were admitted to hospital. We were unable to contact 20% of subjects after their visit. A logistic regression model using continuous oxygen saturation, respiratory rate, temperature and age combined with dichotomous signs of chest indrawing, lethargy, irritability and symptoms of cough, diarrhea and fast or difficult breathing predicted admission to hospital with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval -CI: 0.87 to 0.90). At a risk threshold of 25% for admission, the sensitivity was 77% (95% CI: 74% to 80%), specificity was 87% (95% CI: 86% to 88%), positive predictive value was 70% (95% CI: 67% to 73%) and negative predictive value was 91% (95% CI: 90% to 92%)., Conclusion: A model using oxygen saturation, respiratory rate and temperature in combination with readily obtained clinical signs and symptoms predicted the need for hospitalization of critically ill children. External validation of this model in a community setting will be required before adoption into clinical practice.

Background: Children discharged from hospitals in developing countries are at high risk of morbidity and mortality. However, few data describe these outcomes among children seen and discharged from rural outpatient centers., Objective: The objective of this exploratory study was to identify predictors of immediate and follow-up morbidity and mortality among children visiting a rural health center in Uganda., Methods: Subjects 0-12 years of age seeking care with a caregiver were consecutively enrolled from a single rural health center in Southwestern Uganda. Baseline variables were collected by research nurses and outcomes of referral, admission or death were recorded (immediate events). Death, hospital admission and health seeking occurring during the 30 days following the clinic visit were also determined (follow-up events). Univariate logistic regression was performed to identify baseline variables associated with immediate outcome and follow-up outcomes., Results: Over the four-month recruitment period 717 subjects were enrolled. There were 85 (11.9%) immediate events (10.1% were admitted, 2.2% were referred, none died). Forty-seven (7.8%) events occurred within 30 days after the visit (7.3% sought care from a health provider, 1.5% were admitted and 0.5% died). Variables associated with immediate events included living more than 30 minutes from the health center, age older than 5 years, having received an antimalarial prior to the visit, having seen a community health worker prior to the visit, elevated respiratory rate or temperature, and depressed weight-for-age z score or decreased oxygen saturation. These variables were not associated with follow-up events., Conclusions: Sick-child visits at a rural health center in South Western Uganda were associated with rates of mortality and subsequent admission of less than 2% in the period following the sick child visits. Other types of health seeking behavior occurred in approximately 7% of subjects during this same period. Several variables were associated with immediate events but there were no reliable predictors of follow-up events, possibly due to low statistical power.

Background: Sleep disordered breathing (SDB) can lead to daytime sleepiness, growth failure and developmental delay in children. Polysomnography (PSG), the gold standard to diagnose SDB, is a highly resource-intensive test, confined to the sleep laboratory., Aim: To combine the blood oxygen saturation (SpO2) characterization and cardiac modulation, quantified by pulse rate variability (PRV), to identify children with SDB using the Phone Oximeter, a device integrating a pulse oximeter with a smartphone., Methods: Following ethics approval and informed consent, 160 children referred to British Columbia Children's Hospital for overnight PSG were recruited. A second pulse oximeter sensor applied to the finger adjacent to the one used for standard PSG was attached to the Phone Oximeter to record overnight pulse oximetry (SpO2 and photoplethysmogram (PPG)) alongside the PSG., Results: We studied 146 children through the analysis of the SpO2 pattern, and PRV as an estimate of heart rate variability calculated from the PPG. SpO2 variability and SpO2 spectral power at low frequency, was significantly higher in children with SDB due to the modulation provoked by airway obstruction during sleep (p-value <0.01). PRV analysis reflected a significant augmentation of sympathetic activity provoked by intermittent hypoxia in SDB children. A linear classifier was trained with the most discriminating features to identify children with SDB. The classifier was validated with internal and external cross-validation, providing a high negative predictive value (92.6%) and a good balance between sensitivity (88.4%) and specificity (83.6%). Combining SpO2 and PRV analysis improved the classification performance, providing an area under the receiver operating characteristic curve of 88%, beyond the 82% achieved using SpO2 analysis alone., Conclusions: These results demonstrate that the implementation of this algorithm in the Phone Oximeter will provide an improved portable, at-home screening tool, with the capability of monitoring patients over multiple nights.

The recommended method for measuring respiratory rate (RR) is counting breaths for 60 s using a timer. This method is not efficient in a busy clinical setting. There is an urgent need for a robust, low-cost method that can help front-line health care workers to measure RR quickly and accurately. Our aim was to develop a more efficient RR assessment method. RR was estimated by measuring the median time interval between breaths obtained from tapping on the touch screen of a mobile device. The estimation was continuously validated by measuring consistency (% deviation from the median) of each interval. Data from 30 subjects estimating RR from 10 standard videos with a mobile phone application were collected. A sensitivity analysis and an optimization experiment were performed to verify that a RR could be obtained in less than 60 s; that the accuracy improves when more taps are included into the calculation; and that accuracy improves when inconsistent taps are excluded. The sensitivity analysis showed that excluding inconsistent tapping and increasing the number of tap intervals improved the RR estimation. Efficiency (time to complete measurement) was significantly improved compared to traditional methods that require counting for 60 s. There was a trade-off between accuracy and efficiency. The most balanced optimization result provided a mean efficiency of 9.9 s and a normalized root mean square error of 5.6%, corresponding to 2.2 breaths/min at a respiratory rate of 40 breaths/min. The obtained 6-fold increase in mean efficiency combined with a clinically acceptable error makes this approach a viable solution for further clinical testing. The sensitivity analysis illustrating the trade-off between accuracy and efficiency will be a useful tool to define a target product profile for any novel RR estimation device.

The photoplethysmogram (PPG) obtained from pulse oximetry measures local variations of blood volume in tissues, reflecting the peripheral pulse modulated by heart activity, respiration and other physiological effects. We propose an algorithm based on the correntropy spectral density (CSD) as a novel way to estimate respiratory rate (RR) and heart rate (HR) from the PPG. Time-varying CSD, a technique particularly well-suited for modulated signal patterns, is applied to the PPG. The respiratory and cardiac frequency peaks detected at extended respiratory (8 to 60 breaths/min) and cardiac (30 to 180 beats/min) frequency bands provide RR and HR estimations. The CSD-based algorithm was tested against the Capnobase benchmark dataset, a dataset from 42 subjects containing PPG and capnometric signals and expert labeled reference RR and HR. The RR and HR estimation accuracy was assessed using the unnormalized root mean square (RMS) error. We investigated two window sizes (60 and 120 s) on the Capnobase calibration dataset to explore the time resolution of the CSD-based algorithm. A longer window decreases the RR error, for 120-s windows, the median RMS error (quartiles) obtained for RR was 0.95 (0.27, 6.20) breaths/min and for HR was 0.76 (0.34, 1.45) beats/min. Our experiments show that in addition to a high degree of accuracy and robustness, the CSD facilitates simultaneous and efficient estimation of RR and HR. Providing RR every minute, expands the functionality of pulse oximeters and provides additional diagnostic power to this non-invasive monitoring tool.

Objectives: Mortality following hospital discharge is an important and under-recognized contributor to overall child mortality in developing countries. The primary objective of this systematic review was to identify all studies reporting post-discharge mortality in children, estimate likelihood of death, and determine the most important risk factors for death., Search Strategy: MEDLINE and EMBASE were systematically searched using MeSH terms and keywords from the inception date to October, 2012. Key word searches using Google Scholar™ and hand searching of references of retrieved articles was also performed. Studies from developing countries reporting mortality following hospital discharge among a pediatric population were considered for inclusion., Results: Thirteen studies that reported mortality rates following discharge were identified. Studies varied significantly according to design, underlying characteristics of study population and duration of follow-up. Mortality rates following discharge varied significantly between studies (1%-18%). When reported, post-discharge mortality rates often exceeded in-hospital mortality rates. The most important baseline variables associated with post-discharge mortality were young age, malnutrition, multiple previous hospitalizations, HIV infection and pneumonia. Most post-discharge deaths occurred early during the post-discharge period. Follow-up care was examined in only one study examining malaria prophylaxis in children discharged following an admission secondary to malaria, which showed no significant benefit on post-discharge mortality., Conclusions: The months following hospital discharge carry significant risk for morbidity and mortality. While several characteristics are strongly associated with post-discharge mortality, no validated tools are available to aid health workers or policy makers in the systematic identification of children at high risk of post-discharge mortality. Future research must focus on both the creation of tools to aid in defining groups of children most likely to benefit from post-discharge interventions, and formal assessment of the effectiveness of such interventions in reducing morbidity and mortality in the first few months following hospital discharge.