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Background: Family Integrated Care (FICare) is a model of care developed in a Canadian Neonatal Intensive Care Unit that engages parents to be active participants in their infant’s care team. FICare has the potential to have the greatest impact in low-income countries, where the neonatal mortality rate is disproportionately high and the health workforce is severely strained. This manuscript details the facilitators and constraints that informed the adaptation of FICare to a neonatal hospital unit in Uganda Methods: Focus groups of ten mothers and interviews of eight workers were conducted to identify facilitators and constraints to the implementation of FICare in Uganda. Transcripts were analyzed using inductive content analysis. An adaptation team of key stakeholders developed Uganda FICare in the Special Care Nursery in Jinja Regional Referral Hospital based on the results from the focus groups and interviews. Results: The potential to reduce the healthcare provider workload, the desire to empower mothers and the pursuit to improve neonatal outcomes were identified as key facilitators. Maternal difficulty in learning new skills, lack of trust from healthcare providers and increased maternal stress were cited as potential barriers. Uganda FICare focused on task-shifting important but often neglected patient care tasks from healthcare providers to mothers. Healthcare providers were taught how to respond to maternal concerns. All intervention material was adapted to prioritize images over text. Mothers familiar with FICare were encouraged to provide peer-to-peer support and guidance to mothers with newly hospitalized infants. Conclusions: Engaging stakeholders to identify the facilitators and constraints to local implementation is a key step in adapting an intervention to a new context. Uganda FICare shares the core values of the original FICare but is adapted to enhance its feasibility in low-resource settings.

Supplemental Digital Content is available in the text., Objective: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020. Study Selection: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms “sepsis,” “septicemia,” or “septic shock” in the title or abstract. Data Extraction: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed. Data Synthesis: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001). Conclusions: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

OBJECTIVE: The objective of this narrative review is to outline the current epidemiology and interventional research within the context of sepsis recovery, and to provide a summary of key priorities for future work in this area. BACKGROUND: Morbidity and mortality secondary to sepsis disproportionately affects children, especially those in low- and middle-income countries (LMICs), where over 85% of global cases and deaths occur. These regions are plagued by poorly resilient health systems, widespread socio-economic deprivation and unique vulnerabilities such as malnutrition. Reducing the overall burden of sepsis will require a multi-pronged strategy that addresses all three important periods along the sepsis care continuum - pre-facility, facility and post-facility. Of these aspects, post-facility issues have been largely neglected in research, practice and policy, and are thus the focus of this review. METHODS: Relevant data for this review was identified through a literature search using PubMed, through a review of the citations of select systematic reviews and from the personal repositories of articles collected by the authors. Data is presented within three sections. The first two sections on the short and long-term outcomes among sepsis survivors each outline the epidemiology as well as review relevant interventional research done. Where clear gaps exist, these are stated. The third section focuses on priorities for future research. This section highlights the importance of data (and data systems) and of innovative interventional approaches, as key areas to improve research of post-sepsis outcomes in children. CONCLUSIONS: During the initial post-facility period, mortality is high with as many children dying during this period as during the acute period of hospitalization, mostly due to recurrent illness (including infections) which are associated with malnutrition and severe acute disease. Long-term outcomes, often labelled as post-sepsis syndrome (PSS), are characterized by a lag in developmental milestones and suboptimal quality of life (QoL). While long-term outcomes have not been well characterized in resource limited settings, they are well described in high-income countries (HICs), and likely are important contributors to long-term morbidity in resource limited settings. The paucity of interventional research to improve post-discharge outcomes (short- or long-term) is a clear gap in addressing its burden. A focus on the development of improved data systems for collecting routine data, standardized definitions and terminology and a health-systems approach in research need to be prioritized during any efforts to improve outcomes during the post-sepsis phase.

In low-income and middle-income countries, most patients with febrile illnesses present to peripheral levels of the health system where diagnostic capacity is very limited. In these contexts, accurate risk stratification can be particularly impactful, helping to guide allocation of scarce resources to ensure timely and tailored care. However, reporting of prognostic research is often imprecise and few prognostic tests or algorithms are translated into clinical practice.Here, we review the often-conflated concepts of prognosis and diagnosis, with a focus on patients with febrile illnesses. Drawing on a recent global stakeholder consultation, we apply these concepts to propose three use-cases for prognostic tools in the management of febrile illnesses in resource-limited settings: (1) guiding referrals from the community to higher-level care; (2) informing resource allocation for patients admitted to hospital and (3) identifying patients who may benefit from closer follow-up post-hospital discharge. We explore the practical implications for new technologies and reflect on the challenges and knowledge gaps that must be addressed before this approach could be incorporated into routine care settings.Our intention is that these use-cases, alongside other recent initiatives, will help to promote a harmonised yet contextualised approach for prognostic research in febrile illness. We argue that this is especially important given the heterogeneous settings in which care is often provided for patients with febrile illnesses living in low-income and middle-income countries.

BackgroundThe 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.ObjectiveTo 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 StrategyWe 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 SelectionWe will include observational studies published since January 1, 2005, that meet all eligibility criteria and for which a full text can be located.Data ExtractionData extraction will include information related to study characteristics, hospital characteristics, underlying population characteristics, patient population characteristics, and outcomes.Data SynthesisWe 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.ConclusionsBy 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.

Background Sepsis disproportionately affects children from socioeconomically disadvantaged families in low-resource settings, where care seeking may consume scarce family resources and lead to financial hardships. Those financial hardships may, in turn, contribute to late presentation or failure to seek care and result in high mortality during hospitalization and during the post discharge period, a period of increasingly recognized vulnerability. The purpose of this study is to explore the out-of-pocket costs related to sepsis hospitalizations and post-discharge care among children admitted with sepsis in Uganda. Methods This mixed-methods study was comprised of focus group discussions (FGD) with caregivers of children admitted for sepsis, which then informed a quantitative cross-sectional household survey to measure out-of-pocket costs of sepsis care both during initial admission and during the post-discharge period. All participants were families of children enrolled in a concurrent sepsis study. Results Three FGD with mothers (n = 20) and one FGD with fathers (n = 7) were conducted. Three primary themes that emerged included (1) financial losses, (2) time and productivity losses and (3) coping with costs. A subsequently developed cross-sectional survey was completed for 153 households of children discharged following admission for sepsis. The survey revealed a high cost of care for families attending both private and public facilities, although out-of-pocket cost were higher at private facilities. Half of those surveyed reported loss of income during hospitalization and a third sold household assets, most often livestock, to cover costs. Total mean out-of-pocket costs of hospital care and post-discharge care were 124.50 USD and 44.60 USD respectively for those seeking initial care at private facilities and 62.10 USD and 14.60 USD at public facilities, a high sum in a country with widespread poverty. Conclusions This study reveals that families incur a substantial economic burden in accessing care for children with sepsis.

Background Standardized collection of predictors of pediatric sepsis has enormous potential to increase data compatibility across research studies. The Pediatric Sepsis Predictor Standardization Working Group collaborated to define common data elements for pediatric sepsis predictors at the point of triage to serve as a standardized framework for data collection in resource-limited settings. Methods A preliminary list of pediatric sepsis predictor variables was compiled through a systematic literature review and examination of global guideline documents. A 5-round modified Delphi that involved independent voting and active group discussions was conducted to select, standardize, and prioritize predictors. Considerations included the perceived predictive value of the candidate predictor at the point of triage, intra- and inter-rater measurement reliability, and the amount of time and material resources required to reliably collect the predictor in resource-limited settings. Results We generated 116 common data elements for implementation in future studies. Each common data element includes a standardized prompt, suggested response values, and prioritization as tier 1 (essential), tier 2 (important), or tier 3 (exploratory). Branching logic was added to the predictors list to facilitate the design of efficient data collection methods, such as low-cost electronic case report forms on a mobile application. The set of common data elements are freely available on the Pediatric Sepsis CoLab Dataverse and a web-based feedback survey is available through the Pediatric Sepsis CoLab. Updated iterations will continuously be released based on feedback from the pediatric sepsis research community and emergence of new information. Conclusion Routine use of the common data elements in future studies can allow data sharing between studies and contribute to development of powerful risk prediction algorithms. These algorithms may then be used to support clinical decision making at triage in resource-limited settings. Continued collaboration, engagement, and feedback from the pediatric sepsis research community will be important to ensure the common data elements remain applicable across a broad range of geographical and sociocultural settings.

BackgroundThe 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.MethodsWe 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.DiscussionThis 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.

Background Sepsis is the leading cause of death and disability in children. Every hour of delay in treatment is associated with an escalating risk of morbidity and mortality. The burden of sepsis is greatest in low- and middle-income countries where timely treatment may not occur due to delays in diagnosis and prioritization of critically ill children. To circumvent these challenges, we propose the development and clinical evaluation of a digital triage tool that will identify high risk children and reduce time to treatment. We will also implement and clinically validate a Radio-Frequency Identification system to automate tracking of patients. The mobile platform (mobile device and dashboard) and automated patient tracking system will create a low cost, highly scalable solution for critically ill children, including those with sepsis. Methods This is pre-post intervention study consisting of three phases. Phase I will be a baseline period where data is collected on key predictors and outcomes before implementation of the digital triage tool. In Phase I, there will be no changes to healthcare delivery processes in place at the study hospitals. Phase II will involve model derivation, technology development, and usability testing. Phase III will be the intervention period where data is collected on key predictors and outcomes after implementation of the digital triage tool. The primary outcome, time to treatment initiation, will be compared to assess effectiveness of the digital health intervention. Discussion Smart technology has the potential to overcome the barrier of limited clinical expertise in the identification of the child at risk. This mobile health platform, with sensors and data-driven applications, will provide real-time individualized risk prediction to rapidly triage patients and facilitate timely access to life-saving treatments for children in low- and middle-income countries, where specialists are not regularly available and deaths from sepsis are common. Trial registration Clinical Trials.gov Identifier: NCT04304235, Registered 11 March 2020.

Background: Over two-thirds of the five million annual deaths in children under five occur in infants, mostly in developing countries and many after hospital discharge. However, there is a lack of understanding of which children are at higher risk based on early clinical predictors. Early identification of vulnerable infants at high-risk for death post-discharge is important in order to craft interventional programs. Objectives: To determine potential predictor variables for post-discharge mortality in infants less than one year of age who are likely to die after discharge from health facilities in the developing world. Methods: A two-round modified Delphi process was conducted, wherein a panel of experts evaluated variables selected from a systematic literature review. Variables were evaluated based on (1) predictive value, (2) measurement reliability, (3) availability, and (4) applicability in low-resource settings. Results: In the first round, 18 experts evaluated 37 candidate variables and suggested 26 additional variables. Twenty-seven variables derived from those suggested in the first round were evaluated by 17 experts during the second round. A final total of 55 candidate variables were retained. Conclusion: A systematic approach yielded 55 candidate predictor variables to use in devising predictive models for post-discharge mortality in infants in a low-resource setting. Keywords: Candidate predictor variables, pediatrics, neonatal, infants, prediction, post-discharge mortality, sepsis.

Summary Background Selection of optimal second-line antiretroviral therapy (ART) has important clinical and programmatic implications. To inform the 2016 revision of the WHO ART guidelines, we assessed the comparative effectiveness and safety of available second-line ART regimens for adults and adolescents in whom first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have failed. Methods In this systematic review and network meta-analysis, we searched for randomised controlled trials and prospective and retrospective cohort studies that evaluated outcomes in treatment-experienced adults living with HIV who switched ART regimen after failure of a WHO-recommended first-line NNRTI-based regimen. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials for reports published from Jan 1, 1996, to Aug 8, 2016, and searched conference abstracts published from Jan 1, 2014, to Aug 8, 2016. Outcomes of interest were viral suppression, mortality, AIDS-defining illnesses or WHO stage 3–4 disease, discontinuations, discontinuations due to adverse events, and serious adverse events. We assessed comparative efficacy and safety in a network meta-analysis, using Bayesian hierarchical models. Findings We identified 12 papers pertaining to eight studies, including 4778 participants. The network was centred on ritonavir-boosted lopinavir plus two nucleoside or nucleotide reverse transcriptase inhibitors. Ritonavir-boosted lopinavir monotherapy was the only regimen inferior to others. With the lower estimate of the 95% credible interval (CrI) not exceeding the predefined threshold of 15%, evidence at 48 weeks supported the non-inferiority of ritonavir-boosted lopinavir plus raltegravir to regimens including ritonavir-boosted protease inhibitor plus two NRTIs with respect to viral suppression (odds ratio 1·09, 95% CrI 0·88–1·35). Estimated efficacy of ritonavir-boosted darunavir (800 mg once daily) was too imprecise to determine non-inferiority. Overall, regimens did not differ significantly with respect to continuations, AIDS-defining illnesses or WHO stage 3–4 disease, or mortality. Interpretation With the exception of ritonavir-boosted lopinavir plus raltegravir, the evidence base is unable to provide strong support to alternative second-line options to ritonavir-boosted protease inhibitor plus two NRTIs, and thus more trials are warranted. Funding WHO.

IntroductionThe burden of childhood mortality continues to be born largely by low-income and middle-income countries. The critical postdischarge period has been largely neglected despite evidence that mortality rates during this period can exceed inpatient mortality rates. However, there is a paucity of data on the paediatric discharge process from the perspective of the healthcare provider. Provider perspectives may be important in the development of an improved understanding of the barriers and facilitators to improving the transition from hospital to home.ObjectivesTo explore healthcare providers’ and facility administrators’ perspectives of the paediatric discharge process with respect to: (1) current procedures, (2) barriers and challenges, (3) ideas for change, (4) facilitators for change and (5) the importance of discharge planning.DesignA qualitative exploratory approach using focus groups (14) and in-depth interviews (7).SettingThis study was conducted at seven hospitals providing paediatric care in Uganda.ResultsCurrent discharge procedures are largely based on hospital-specific protocols or clinician opinion, as opposed to national guidelines. Some key barriers to an improved discharge process included caregiver resources and education, critical communication gaps, traditional practices, and a lack of human and physical resources. Teamwork and motivation to see improved paediatric transitions to home were identified as facilitators to implementing the ideas for change proposed by participants. The need for a standardised national policy guiding paediatric discharges, implemented through education at many levels and coupled with appropriate community referral and follow-up, was broadly perceived as essential to improving outcomes for children.ConclusionsAlthough significant challenges and gaps were identified within the current health system, participants’ ideas and the identified facilitators provide a significant basis from which change may occur. This work can facilitate the development of sustainable and effective interventions to improve postdischarge outcomes in Uganda and other similar settings.

Background: Many hospitalized children in developing countries die from infectious diseases. Early recognition of those who are critically ill coupled with timely treatment can prevent many deaths. A data-driven, electronic triage system to assist frontline health workers in categorizing illness severity is lacking. This study aimed to develop a data-driven parsimonious triage algorithm for children under five years of age. Methods: This was a prospective observational study of children under-five years of age presenting to the outpatient department of Mbagathi Hospital in Nairobi, Kenya between January and June 2018. A study nurse examined participants and recorded history and clinical signs and symptoms using a mobile device with an attached low-cost pulse oximeter sensor. The need for hospital admission was determined independently by the facility clinician and used as the primary outcome in a logistic predictive model. We focused on the selection of variables that could be quickly and easily assessed by low skilled health workers. Results: The admission rate (for more than 24 hours) was 12% (N=138/1,132). We identified an eight-predictor logistic regression model including continuous variables of weight, mid-upper arm circumference, temperature, pulse rate, and transformed oxygen saturation, combined with dichotomous signs of difficulty breathing, lethargy, and inability to drink or breastfeed. This model predicts overnight hospital admission with an area under the receiver operating characteristic curve of 0.88 (95% CI 0.82 to 0.94). Low- and high-risk thresholds of 5% and 25%, respectively were selected to categorize participants into three triage groups for implementation. Conclusion: A logistic regression model comprised of eight easily understood variables may be useful for triage of children under the age of five based on the probability of need for admission. This model could be used by frontline workers with limited skills in assessing children. External validation is needed before adoption in clinical practice.

BackgroundAfrica has the highest rates of child mortality. Little is known about outcomes after hospitalization for children with very severe anemia.ObjectiveTo determine one year mortality and predictors of mortality in Tanzanian children hospitalized with very severe anemia.MethodsWe conducted a prospective cohort study enrolling children 2-12 years hospitalized from August 2014 to November 2014 at two public hospitals in northwestern Tanzania. Children were screened for anemia and followed until 12 months after discharge. The primary outcome measured was mortality. Predictors of mortality were determined using Cox regression analysis.ResultsOf the 505 children, 90 (17.8%) had very severe anemia and 415 (82.1%) did not. Mortality was higher for children with very severe anemia compared to children without over a one year period from admission, 27/90 (30.0%) vs. 59/415 (14.2%) respectively (Hazard Ratio (HR) 2.42, 95% Cl 1.53–3.83). In-hospital mortality was 11/90 (12.2%) and post-hospital mortality was 16/79 (20.2%) for children with very severe anemia. The strongest predictors of mortality were age (HR 1.01, 95% Cl 1.00–1.03) and decreased urine output (HR 4.30, 95% Cl 1.04 – 17.7).ConclusionsChildren up to 12 years of age with very severe anemia have nearly a 30% chance of mortality following admission over a one year period, with over 50% of mortality occurring after discharge. Post-hospital interventions are urgently needed to reduce mortality in children with very severe anemia, and should include older children.

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.

ObjectivesTo update the current evidence base on paediatric postdischarge mortality (PDM) in developing countries. Secondary objectives included an evaluation of risk factors, timing and location of PDM.DesignSystematic literature review without meta-analysis.Data sourcesSearches of Medline and EMBASE were conducted from October 2012 to July 2017.Eligibility criteriaStudies were included if they were conducted in developing countries and examined paediatric PDM. 1238 articles were screened, yielding 11 eligible studies. These were added to 13 studies identified in a previous systematic review including studies prior to October 2012. In total, 24 studies were included for analysis.Data extraction and synthesisTwo independent reviewers extracted and synthesised data using Microsoft Excel.ResultsStudies were conducted mostly within African countries (19 of 24) and looked at all admissions or specific subsets of admissions. The primary subpopulations included malnutrition, respiratory infections, diarrhoeal diseases, malaria and anaemia. The anaemia and malaria subpopulations had the lowest PDM rates (typically 1%–2%), while those with malnutrition and respiratory infections had the highest (typically 3%–20%). Although there was significant heterogeneity between study populations and follow-up periods, studies consistently found rates of PDM to be similar, or to exceed, in-hospital mortality. Furthermore, over two-thirds of deaths after discharge occurred at home. Highly significant risk factors for PDM across all infectious admissions included HIV status, young age, pneumonia, malnutrition, anthropometric variables, hypoxia, anaemia, leaving hospital against medical advice and previous hospitalisations.ConclusionsPostdischarge mortality rates are often as high as in-hospital mortality, yet remain largely unaddressed. Most children who die following discharge do so at home, suggesting that interventions applied prior to discharge are ideal to addressing this neglected cause of mortality. The development, therefore, of evidence-based, risk-guided, interventions must be a focus to achieve the sustainable development goals.

Post-hospital discharge is a vulnerable time for recurrent illness and death among children. An intervention package consisting of (1) referrals for scheduled follow-up visits, (2) discharge counseling, and (3) simple prevention items such as soap and oral rehydration salts resulted in much higher health seeking and hospital readmissions compared with historical controls., Background: Recurrent illness following hospital discharge is a major contributor to childhood mortality in resource-poor countries. Yet post-discharge care is largely ignored by health care workers and policy makers due to a lack of resources to identify children with recurrent illness and a lack of cohesive systems to provide care. The purpose of this proof-of-concept study was to evaluate the effectiveness of a bundle of interventions at discharge to improve health outcomes during the vulnerable post-discharge period. Methods: The study was conducted between December 2014 and April 2015. Eligible children were between ages 6 months and 5 years who were admitted with a suspected or proven infectious disease to one of two hospitals in Mbarara, Uganda. A bundle of interventions was provided at the time of discharge. This bundle included post-discharge referrals for follow-up visits and a discharge kit. The post-discharge referral was to ensure follow-up with a nearby health care provider on days 2, 7, and 14 following discharge. The discharge kit included brief educational counseling along with simple preventive items as incentives (soap, a mosquito net, and oral rehydration salts) to reinforce the education. The primary study outcome was the number of post-discharge referral visits completed. Secondary study outcomes included satisfaction with the intervention, rates of readmission after 60 days, and post-discharge mortality rates. In addition, outcomes were compared with a historical control group, enrolled using the same inclusion criteria and outcome-ascertainment methods. Results: During the study, 216 children were admitted, of whom 14 died during hospitalization. Of the 202 children discharged, 85% completed at least 1 of the 3 follow-up referral visits, with 48% completing all 3 visits. Within 60 days after discharge, 22 children were readmitted at least once and 5 children (2.5%) died. Twelve (43%) readmissions occurred during a scheduled follow-up visit. Compared with prospectively enrolled historical controls, the post-discharge referral for follow-up increased the odds of readmission (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.14 to 3.23) and care sought after discharge (OR, 14.61; 95% CI, 9.41 to 22.67). Overall satisfaction with the bundle of interventions was high, with most caregivers strongly agreeing that the discharge kit and post-discharge referrals improved their ability to care for their child. Conclusions: Interventions initiated at the time of discharge have the potential to profoundly affect the landscape of care during illness recovery and lead to significantly improved outcomes among children under 5 years of age.

Acute infectious diseases are the most common cause of under-5 mortality. However, the hospital burden of nonneonatal pediatric sepsis has not previously been described in the resource poor setting. The objective of this study was to determine the prevalence of sepsis among children 6 months to 5 years old admitted with proven or suspected infection and to evaluate the presence of sepsis as a predictive tool for mortality during admission.In this prospective cohort study, we used the pediatric International Consensus Conference definition of sepsis to determine the prevalence of sepsis among children admitted to the pediatric ward with a proven or suspected infection. The diagnosis of sepsis, as well as each individual component of the sepsis definition, was evaluated for capturing in-hospital mortality.The pediatric ward of two hospitals in Mbarara, Uganda.Admitted children between 6 months and 5 years with a confirmed or suspected infection.None.One thousand three hundred seven (1,307) subjects with a confirmed or suspected infection were enrolled, and 65 children died (5.0%) during their admission. One thousand one hundred twenty-one (85.9%) met the systemic inflammatory response syndrome criteria, and therefore, they were defined as having sepsis. The sepsis criteria captured 61 deaths, demonstrating a sensitivity and a specificity of 95% (95% CI, 90-100%) and 15% (95% CI, 13-17%), respectively. The most discriminatory individual component of the systemic inflammatory response syndrome criteria was the leukocyte count, which alone had a sensitivity of 72% and a specificity of 56% for the identification of mortality in hospital.This study is among the first to quantify the burden of nonneonatal pediatric sepsis in children with suspected infection, using the international consensus sepsis definition, in a typical resource-constrained setting in Africa. This definition was found to be highly sensitive in identifying those who died but had very low specificity as most children who were admitted with infections had sepsis. The systemic inflammatory response syndrome-based sepsis definition offers little value in identification of children at high risk of in-hospital mortality in this setting.

Conducting collaborative and comprehensive epidemiological research on neonatal sepsis in low- and middle-income countries (LMICs) is challenging due to a lack of diagnostic tests. This prospective study protocol aims to obtain epidemiological data on bacterial sepsis in newborns and young infants at Kamuzu Central Hospital in Lilongwe, Malawi. The main goal is to determine if the use of whole blood transcriptome host immune response signatures can help in the identification of infants who have sepsis of bacterial causes. The protocol includes a detailed clinical assessment with vital sign measurements, strict aseptic blood culture protocol with state-of-the-art microbial analyses and RNA-sequencing and metagenomics evaluations of host responses and pathogens, respectively. We also discuss the directions of a brief analysis plan for RNA sequencing data. This study will provide robust epidemiological data for sepsis in neonates and young infants in a setting where sepsis confers an inordinate burden of disease.

BackgroundSepsis 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.ObjectiveThis 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 designThe 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.ResultsThere 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).ConclusionA 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.

Conducting collaborative and comprehensive epidemiological research on neonatal sepsis in low- and middle-income countries (LMICs) is challenging due to a lack of diagnostic tests. This prospective study protocol aims to obtain epidemiological data on bacterial sepsis in newborns and young infants at Kamuzu Central Hospital in Lilongwe, Malawi. The main goal is to determine if the use of whole blood transcriptome host immune response signatures can help in the identification of infants who have sepsis of bacterial causes. The protocol includes a detailed clinical assessment with vital sign measurements, strict aseptic blood culture protocol with state-of-the-art microbial analyses and RNA-sequencing and metagenomics evaluations of host responses and pathogens, respectively. We also discuss the directions of a brief analysis plan for RNA sequencing data. This study will provide robust epidemiological data for sepsis in neonates and young infants in a setting where sepsis confers an inordinate burden of disease.

We evaluated the association between HIV exposed-uninfected (HEU) status, malnutrition and risk of death in Ugandan children hospitalized with pneumonia. Both HIV exposure and infection were associated with lower anthropometric indices on univariate analysis, and mid-upper arm circumference was significantly associated with overall mortality (odds ratio (OR), 0.96) in a multivariable model. HIV infection (OR 5.0) but not HEU status was associated with overall mortality. Malnutrition may contribute to poor pneumonia outcomes among HIV-infected and HEU children requiring hospitalization.

Not much is known about clinical decision-making in rural, low-resource settings regarding fever, a common reason for presentation to care. In this prospective cohort study of patients presenting with febrile illness to a rural Ugandan health center, we examined demographic and clinical factors predictive of an initial disposition of inpatient admission after clinical evaluation, but before laboratory testing. We then assessed the association of laboratory results and system factors with a change between initial and final disposition plans. Four thousand nine hundred twenty-four patients with suspected febrile illness were included in the primary analysis. The strongest predictors for an initial disposition of admission after clinical examination were impaired consciousness (adjusted risk ratio [aRR], 3.21; 95% confidence interval [CI]: 2.44-4.21) and fever on examination (aRR, 2.27; 95% CI: 1.79-2.87). Providers initially planned to discharge patients with significant vital sign abnormalities, including tachypnea (3.6%) and hypotension (1.3%). Anemia strongly predicted a final disposition of admission after an initial disposition of discharge (aRR, 48.34; 95% CI: 24.22-96.49); other laboratory abnormalities, including hypoglycemia and acidosis, did not change disposition planning. In those with an initial disposition of admission, living farther than the two neighboring villages was associated with a final disposition of discharge (aRR, 2.12; 95% CI: 1.10-4.12). A concerning number of patients with abnormal vital signs and laboratory results were not admitted for inpatient care. Geographic factors may influence a patient's final disposition contrary to a provider's initial disposition plan. Future work should assess longer term outcomes after discharge and a broader study population.

BACKGROUND Electronic healthcare records(EHR) are especially important in low-resource settings due to their potential to address unique challenges such as the high numbers of requiring long-term treatments who are lost to follow-up, the frequent shortages of essential drugs, poor maintenance and storage of records and inefficient clinical triaging. However, there is a lack of affordable solutions and many challenges in successfully implementing EHRs in low OBJECTIVE To create a locally-developed electronic healthcare record system tailored to the specific context and needs of Ugandan hospitals. METHODS Stre@mline is an EHR platform that has been locally developed by Ugandan clinicians and engineers in Southwestern Uganda. It is tailored to the specific context and the needs of low-resource hospitals. It operates without internet access, incorporates locally relevant standards and key patient safety features, has a medication inventory management component, has local technical support available, and is economically sustainable without funding from international donors. RESULTS Stre@mline is currently used by over 60 000 patients at 2 hospitals, with plans to expand across Uganda. User surveys from Kisiizi Hospital indicate that the vast majority of Stre@mline users find it is easy to use and helpful in increasing clinical efficiency as well as enhancing patient care. CONCLUSIONS The partnership of local clinicians and developers is crucial to the design and adoption of user-centered technologies tailored to the specific needs of low-resource settings. The EHR described here could serve as a model for the development of future appropriate technologies in developing countries.

Chagas disease is a neglected parasitic illness affecting approximately 8 million people, predominantly in Latin America. Benznidazole is the drug of choice for treatment, although its availability has been limited. A paucity of knowledge of the pharmacokinetic properties of this drug has contributed to its limited availability in several jurisdictions. The objective of this study was to conduct a systematic literature review and a Bayesian meta-analysis of pharmacokinetic studies to improve estimates of the basic pharmacokinetic properties of benznidazole. A systematic search of the Embase, Medline, LILACS, and SciELO (Scientific Electronic Library Online) databases was conducted. Eligible studies reported patient-level data from single-100-mg-dose pharmacokinetic evaluations of benznidazole in adults or otherwise provided data relevant to the estimation of pharmacokinetic parameters which could be derived from such studies. A Bayesian hierarchical model was used for analysis. Secondary data (i.e., data from studies that did not include patient-level, single-100-mg-dose data) were used for the generation of empirical priors for the Bayesian analysis. The systematic search identified nine studies for inclusion. Nine pharmacokinetic parameters were estimated, including the area under the concentration-time curve (AUC), the maximum concentration of drug in plasma ( C max ), the time to C max , the elimination rate constant ( k el ), the absorption rate constant ( K a ), the absorption and elimination half-lives, the apparent oral clearance, and the apparent oral volume of distribution. The results showed consistency across studies. AUC and C max were 51.31 mg · h/liter (95% credible interval [CrI], 45.01, 60.28 mg · h/liter) and 2.19 mg/liter (95% CrI, 2.06, 2.33 mg/liter), respectively. K a and k el were 1.16 h −1 (95% CrI, 0.59, 1.76 h −1 ) and 0.052 h −1 (95% CrI, 0.045, 0.059 h −1 ), respectively, with the corresponding absorption and elimination half-lives being 0.60 h (95% CrI, 0.38, 1.11 h) and 13.27 h (95% CrI, 11.79, 15.42 h), respectively. The oral clearance and volume of distribution were 2.04 liters/h (95% CrI, 1.77, 2.32 liters/h) and 39.19 liters (95% CrI, 36.58, 42.17 liters), respectively. A Bayesian meta-analysis was used to improve the estimates of the standard pharmacokinetic parameters of benznidazole. These data can inform clinicians and policy makers as access to this drug increases.

KEY POINTS The failure to recognize and treat the child with sepsis is devastating to the child and family, as well as for physicians, other health care providers and policy-makers. Several recent high-profile deaths from sepsis in Canadian children1 have highlighted the need for rapid and reliable