Hydroxyurea reduces infections in children with sickle cell anemia in Uganda.

ABSTRACT: After starting hydroxyurea treatment, Ugandan children with sickle cell anemia had 60% fewer severe or invasive infections, including malaria, bacteremia, respiratory tract infections, and gastroenteritis, than before starting hydroxyurea treatment (incidence rate ratio, 0.40 [95% confidence interval, 0.29-0.54]; P < .001).

Facilitators and constraints to family integrated care in low-resource settings informed the adaptation in Uganda.

AIM: Family Integrated Care (FICare) was developed in high-income countries and has not been tested in resource-poor settings. We aimed to identify the facilitators and constraints that informed the adaptation of FICare to a neonatal hospital unit in Uganda. METHODS: Maternal focus groups and healthcare provider interviews were conducted at Uganda's Jinja Regional Referral Hospital in 2020. Transcripts were analysed using inductive content analysis. An adaptation team developed Uganda FICare based on the identified facilitators and constraints. RESULTS: Participants included 10 mothers (median age 28 years) and eight healthcare providers (seven female, median age 41 years). Reducing healthcare provider workload, improving neonatal outcomes and empowering mothers were identified as facilitators. Maternal stress, maternal difficulties in learning new skills and mistrust of mothers by healthcare providers were cited as constraints. Uganda FICare focused on task-shifting important but neglected patient care tasks from healthcare providers to mothers. Healthcare providers learned how to respond to maternal concerns. Intervention material was adapted to prioritise images over text. Mothers familiar with FICare provided peer-to-peer support to other mothers. CONCLUSION: Uganda FICare shares the core values of FICare but was adapted to be feasible in low-resource settings.

Benefits and Challenges of Implementing an Adaptation of Family Integrated Care in a Ugandan Setting.

BACKGROUND: Family Integrated Care (FICare) integrates parents as partners in neonatal intensive care unit care. Our team adapted and implemented this approach in a Ugandan unit for hospitalized neonates. PURPOSE: This qualitative descriptive study examined the perceptions of mothers and healthcare professionals (HCPs) of the benefits and challenges of this new approach to care. METHODS: Fifty-one mothers of hospitalized neonates born weighing greater than 2000 g participated in the program. They were taught to assess neonate danger signs, feeding, and weight. After discharge, a subsample (n = 15) participated in focus groups to explore benefits and challenges of their participation in care. Interviews with 8 HCPs were also conducted for the same purpose. Transcripts from focus groups and interviews were analyzed using inductive content analysis to describe the benefits and challenges from the perspectives of mothers and HCPs. RESULTS: For mothers a benefit was decreased stress. Both mothers and HCPs reported that the knowledge and skills mothers acquired were a benefit as was their ability to apply these to the care of their neonate. Improved relations between mothers and HCPs were described, characterized by greater exchange of information and HCPs' attentiveness to mothers' assessments. Mothers felt ready for discharge and used their knowledge at home. HCPs noted a decrease in their workload. Challenges included the need for mothers to overcome fears about performing the tasks, their own well-being and literacy skills, and access to equipment. IMPLICATIONS FOR PRACTICE: Mothers' participation in their neonates' care can have benefits for them and their neonate.

Cost-effectiveness analysis of Smart Triage, a data-driven pediatric sepsis triage platform in Eastern Uganda.

BACKGROUND: Sepsis, characterized by organ dysfunction due to presumed or proven infection, has a case-fatality over 20% in severe cases in low-and-middle income countries. Early diagnosis and treatment have proven benefits, prompting our implementation of Smart Triage at Jinja Regional Referral Hospital in Uganda, a program that expedites treatment through a data-driven triage platform. We conducted a cost-effectiveness analysis of Smart Triage to explore its impact on patients and inform multicenter scale up. METHODS: The parent clinical trial for Smart Triage was pre-post in design, using the proportion of children receiving sepsis treatment within one hour as the primary outcome, a measure linked to mortality benefit in existing literature. We used a decision-analytic model with Monte Carlo simulation to calculate the cost per year-of-life-lost (YLL) averted of Smart Triage from societal, government, and patient perspectives. Healthcare utilization and lost work for seven days post-discharge were translated into costs and productivity losses via secondary linkage data. RESULTS: In 2021 United States dollars, Smart Triage requires an annuitized program cost of only $0.05 per child, but results in $15.32 saved per YLL averted. At a willingness-to-pay threshold of only $3 per YLL averted, well below published cost-effectiveness threshold estimates for Uganda, Smart Triage approaches 100% probability of cost-effectiveness over the baseline manual triage system. This cost-effectiveness was observed from societal, government, and patient perspectives. The cost-effectiveness observed was driven by a reduction in admission that, while explainable by an improved triage mechanism, may also be partially attributable to changes in healthcare utilization influenced by the coronavirus pandemic. However, Smart Triage remains cost-effective in sensitivity analyses introducing a penalty factor of up to 50% in the reduction in admission. CONCLUSION: Smart Triage's ability to both save costs and avert YLLs indicates that patients benefit both economically and clinically, while its high probability of cost-effectiveness strongly supports multicenter scale up. Areas for further research include the incorporation of years lived with disability when sepsis disability weights in low-resource settings become available and analyzing budget impact during multicenter scale up. TRIAL REGISTRATION: NCT04304235 (registered on 11/03/2020, clinicaltrials.gov).

Health worker perspectives of Smart Triage, a digital triaging platform for quality improvement at a referral hospital in Uganda: a qualitative analysis.

BACKGROUND: Effective triage at hospitals can improve outcomes for children globally by helping identify and prioritize care for those most at-risk of death. Paper-based pediatric triage guidelines have been developed to support frontline health workers in low-resource settings, but these guidelines can be challenging to implement. Smart Triage is a digital triaging platform for quality improvement (QI) that aims to address this challenge. Smart Triage represents a major cultural and behavioural shift in terms of managing patients at health facilities in low-and middle-income countries. The purpose of this study is to understand user perspectives on the usability, feasibility, and acceptability of Smart Triage to inform ongoing and future implementation. METHODS: This was a descriptive qualitative study comprising of face-to-face interviews with health workers (n = 15) at a regional referral hospital in Eastern Uganda, conducted as a sub-study of a larger clinical trial to evaluate Smart Triage (NCT04304235). Thematic analysis was used to assess the usability, feasibility, and acceptability of the platform, focusing on its use in stratifying and prioritizing patients according to their risk and informing QI initiatives implemented by health workers. RESULTS: With appropriate training and experience, health workers found most features of Smart Triage usable and feasible to implement, and reported the platform was acceptable due to its positive impact on reducing the time to treatment for emergency pediatric cases and its use in informing QI initiatives within the pediatric ward. Several factors that reduced the feasibility and acceptability were identified, including high staff turnover, a lack of medical supplies at the hospital, and challenges with staff attitudes. CONCLUSION: Health workers can use the Smart Triage digital triaging platform to identify and prioritize care for severely ill children and improve quality of care at health facilities in low-resource settings. Future innovation is needed to address identified feasibility and acceptability challenges; however, this platform could potentially address some of the challenges to implementing current paper-based systems.

A 2-Phase Survey to Assess a Facility's Readiness for Pediatric Essential Emergency and Critical Care in Resource-Limited Settings: A Literature Review and Survey Development.

OBJECTIVE: Infectious diseases, including pneumonia, malaria, and diarrheal diseases, are the leading causes of death in children younger than 5 years worldwide. The vast majority of these deaths occur in resource-limited settings where there is significant variation in the availability and type of human, physical, and infrastructural resources. The ability to identity gaps in healthcare systems that may hinder their ability to deliver care is an important step to determining specific interventions for quality improvement. Our study objective was to develop a comprehensive, digital, open-access health facility survey to assess facility readiness to provide pediatric critical care in resource-limited settings (eg, low- and lower middle-income countries). METHODS: A literature review of existing facility assessment tools and global guidelines was conducted to generate a database of survey questions. These were then mapped to one of the following 8 domains: hospital statistics, services offered, operational flow, facility infrastructure, staff and training, medicines and equipment, diagnostic capacity, and quality of clinical care. A 2-phase survey was developed and an iterative review process of the survey was undertaken with 12 experts based in low- and middle-income countries. This was built into the REDCap Mobile Application for electronic data capture. RESULTS: The literature review process yielded 7 facility assessment tools and 7 global guidelines for inclusion. After the iterative review process, the final survey consisted of 11 sections with 457 unique questions in the first phase, "environmental scan," focusing on the infrastructure, availability, and functionality of resources, and 3 sections with 131 unique questions in the second phase, "observation scan," focusing on the level of clinical competency. CONCLUSIONS: A comprehensive 2-phase survey was created to evaluate facility readiness for pediatric critical care. Results will assist hospital administrators and policymakers to determine priority areas for quality improvement, enabling them to implement a Plan-Do-Study-Act cycle to improve care for the critically ill child.

The age-specific incidence of hospitalized paediatric malaria in Uganda.

BACKGROUND: Understanding the relationship between malaria infection risk and disease outcomes represents a fundamental component of morbidity and mortality burden estimations. Contemporary data on severe malaria risks among populations of different parasite exposures are scarce. Using surveillance data, we compared rates of paediatric malaria hospitalisation in areas of varying parasite exposure levels. METHODS: Surveillance data at five public hospitals; Jinja, Mubende, Kabale, Tororo, and Apac were assembled among admissions aged 1 month to 14 years between 2017 and 2018. The address of each admission was used to define a local catchment population where national census data was used to define person-year-exposure to risk. Within each catchment, historical infection prevalence was assembled from previously published data and current infection prevalence defined using 33 population-based school surveys among 3400 children. Poisson regression was used to compute the overall and site-specific incidences with 95% confidence intervals. RESULTS: Both current and historical Plasmodium falciparum prevalence varied across the five sites. Current prevalence ranged from < 1% in Kabale to 54% in Apac. Overall, the malaria admission incidence rate (IR) was 7.3 per 1000 person years among children aged 1 month to 14 years of age (95% CI: 7.0, 7.7). The lowest rate was described at Kabale (IR = 0.3; 95 CI: 0.1, 0.6) and highest at Apac (IR = 20.3; 95 CI: 18.9, 21.8). There was a correlation between IR across the five sites and the current parasite prevalence in school children, though findings were not statistically significant. Across all sites, except Kabale, malaria admissions were concentrated among young children, 74% were under 5 years. The median age of malaria admissions at Kabale hospital was 40 months (IQR 20, 72), and at Apac hospital was 36 months (IQR 18, 69). Overall, severe anaemia (7.6%) was the most common presentation and unconsciousness (1.8%) the least common. CONCLUSION: Malaria hospitalisation rates remain high in Uganda particularly among young children. The incidence of hospitalized malaria in different locations in Uganda appears to be influenced by past parasite exposure, immune acquisition, and current risks of infection. Interruption of transmission through vector control could influence age-specific severe malaria risk.

Smart triage: triage and management of sepsis in children using the point-of-care Pediatric Rapid Sepsis Trigger (PRST) tool.

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.

Is fat mass a better predictor of 6-month survival than muscle mass among African children aged 6-59 months with severe pneumonia?

BACKGROUND: Pneumonia remains the leading cause of mortality among children under 5 years. Poor nutritional status increases pneumonia mortality. Nutritional status assessed by anthropometry alone does not provide information on which body composition element predicts survival. Body composition proxy measures including arm-fat-area (AFA), arm-muscle-area (AMA), and arm-muscle-circumference (AMC) could be useful predictors. OBJECTIVE: To compare the ability of fat and muscle mass indices to predict 6-month survival among children with severe pneumonia. METHODS: This prospective cohort study was nested in the COAST-Nutrition trial (ISRCTN10829073, 06/06/2018) conducted between June 2020 and October 2022 in Uganda and Kenya. We included children aged 6-59 months hospitalized for severe pneumonia with hypoxemia. Children with severe malnutrition, known chronic lung or cardiac diseases were excluded. Anthropometry and clinical status were assessed at enrolment and at follow-up to day 180. We examined Receiver Operator Characteristic (ROC) curves of fat and muscle mass indices with 6-month survival as the outcome, and compared the areas under the curve (AUCs) using chi-square tests. Cox survival analysis models assessed time-to-mortality. RESULTS: We included 369 participants. The median age was 15-months (IQR 9, 26), and 59.4% (219/369) of participants were male. The baseline measurements were: median MUAC 15.0 cm (IQR 14.0,16.0); arm-fat-area 5.6cm2 (IQR 4.7, 6.8); arm-muscle-area 11.4cm2 (IQR 10.0, 12.7); and arm-muscle-circumference 12.2 cm (IQR 11.5, 12.9). Sixteen (4.3%) participants died and 4 (1.1%) were lost-to-follow-up. The AUC for Arm-Fat-Area was not significantly higher than that for Arm-Muscle-Area and Arm-Muscle-Circumference [AUC 0.77 (95%CI 0.64-0.90) vs. 0.61 (95%CI 0.48-0.74), p = 0.09 and 0.63 (95%CI 0.51-0.75), p = 0.16 respectively], but was not statistically different from MUAC (AUC 0.73 (95%CI 0.62-0.85), p = 0.47). Increase in Arm-Fat-Area and Arm-Muscle-Circumference significantly improved survival [aHR 0.40 (95%CI 0.24-0.64), p = < 0.01 and 0.59 (95%CI 0.36-1.06), p = 0.03 respectively]. Survival prediction using Arm-Fat-Area was not statistically different from that of MUAC (p = 0.54). CONCLUSIONS: Muscle mass did not predict 6-month survival better than fat mass in children with severe pneumonia. Fat mass appears to be a better predictor. Effects of fat and muscle could be considered for prognosis and targeted interventions.

Nutritional supplementation in children with severe pneumonia in Uganda and Kenya (COAST-Nutrition): a phase 2 randomised controlled trial.

Background: Severe pneumonia in African children results in poor long-term outcomes (deaths/readmissions) with undernutrition as a key risk factor. We hypothesised additional energy/protein-rich Ready-to-Use Therapeutic Foods (RUTF) would meet additional nutritional requirements and improve outcomes. Methods: COAST-Nutrition was an open-label Phase 2 randomised controlled trial in children (aged 6 months-12 years) hospitalised with severe pneumonia (and hypoxaemia, SpO2 <92%) in Mbale, Soroti, Jinja, Masaka Regional Referral Hospitals, Uganda and Kilifi County Hospital, Kenya (ISRCTN10829073 (registered 6th June 2018) PACTR202106635355751 (registered 2nd June 2021)). Children were randomised (ratio 1:1) to enhanced nutritional supplementation with RUTF (plus usual diet) for 56 days vs usual diet (control). The primary outcome was change in mid-upper arm circumference (MUAC) at 90 days as a composite with mortality. Secondary outcomes include anthropometric status, mortality, and readmissions at Days 28, 90 and 180. Findings: Between 12 August 2018 and 22 April 2022, 846 eligible children were randomised, 424 to RUTF and 422 to usual diet, and followed for 180-days [12 (1%) lost-to-follow-up]. RUTF supplement was initiated in 417/419 (>99%). By Day 90, there was no significant difference in the composite endpoint (probabilistic index 0.49, 95% CI 0.45-0.53, p = 0.74). Respective 90-day mortality (13/420 3.1% vs 14/421 3.3%) and MUAC increment (0.54 (SD 0.85) vs 0.55 (SD 0.81)) were similar between arms. There was no difference in any anthropometric secondary endpoints to Day 28, 90 or 180 except skinfold thickness at Day 28 and Day 90 was greater in the RUTF arm. Serious adverse events were higher in the RUTF arm (n = 164 vs 108), mainly due to hospital readmission for acute illness (54/387 (14%) vs 37/375 (10%). Interpretation: Our study suggested that nutritional supplementation with RUTF did not improve outcomes to 180 days in children with severe pneumonia. Funding: This trial is part of the EDCTP2 programme (grant number RIA-2016S-1636-COAST-Nutrition) supported by the European Union, and UK Joint Global Health Trials scheme: Medical Research Council, Department for International Development, Wellcome Trust (grant number MR/L004364/1, UK).

Prediction models for post-discharge mortality among under-five children with suspected sepsis in Uganda: A multicohort analysis.

In many low-income countries, over five percent of hospitalized children die following hospital discharge. The lack of available tools to identify those at risk of post-discharge mortality has limited the ability to make progress towards improving outcomes. We aimed to develop algorithms designed to predict post-discharge mortality among children admitted with suspected sepsis. Four prospective cohort studies of children in two age groups (0-6 and 6-60 months) were conducted between 2012-2021 in six Ugandan hospitals. Prediction models were derived for six-months post-discharge mortality, based on candidate predictors collected at admission, each with a maximum of eight variables, and internally validated using 10-fold cross-validation. 8,810 children were enrolled: 470 (5.3%) died in hospital; 257 (7.7%) and 233 (4.8%) post-discharge deaths occurred in the 0-6-month and 6-60-month age groups, respectively. The primary models had an area under the receiver operating characteristic curve (AUROC) of 0.77 (95%CI 0.74-0.80) for 0-6-month-olds and 0.75 (95%CI 0.72-0.79) for 6-60-month-olds; mean AUROCs among the 10 cross-validation folds were 0.75 and 0.73, respectively. Calibration across risk strata was good: Brier scores were 0.07 and 0.04, respectively. The most important variables included anthropometry and oxygen saturation. Additional variables included: illness duration, jaundice-age interaction, and a bulging fontanelle among 0-6-month-olds; and prior admissions, coma score, temperature, age-respiratory rate interaction, and HIV status among 6-60-month-olds. Simple prediction models at admission with suspected sepsis can identify children at risk of post-discharge mortality. Further external validation is recommended for different contexts. Models can be digitally integrated into existing processes to improve peri-discharge care as children transition from the hospital to the community.

Family Integrated Care in Uganda: a feasibility study.

OBJECTIVE: To determine the feasibility of adapting Family Integrated Care to a neonatal hospital unit in a low-income country. DESIGN: Single-centre, pre/post-pilot study of an adapted Family Integrated Care programme in Uganda (UFICare). SETTING: Special Care Nursery at a Ugandan hospital. PATIENTS: Singleton, inborn neonates with birth weight ≥2 kg. INTERVENTIONS: As part of UFICare, mothers weighed their infant daily, assessed for severe illness ('danger signs') twice daily and tracked feeds. MAIN OUTCOME MEASURES: Feasibility outcomes included maternal proficiency and completion of monitoring tasks. Secondary outcomes included maternal stress, discharge readiness and post-discharge healthcare seeking. RESULTS: Fifty-three mother-infant dyads and 51 mother-infant dyads were included in the baseline and intervention groups, respectively. Most mothers were proficient in the tasks 2-4 days after training (weigh 43 of 51; assess danger signs 49 of 51; track feeds 49 of 51). Mothers documented their danger sign assessments 82% (IQR 71-100) of the expected times and documented feeds 83% (IQR 71-100) of hospital days. In the baseline group, nurses weighed babies 29% (IQR 18-50) of hospitalised days, while UFICare mothers weighed their babies 71% (IQR 57-80) of hospitalised days (p<0.001). UFICare mothers had higher Readiness for Discharge scores compared with the baseline group (baseline 6.8; UFICare 7.9; p<0.001). There was no difference in maternal stress scores or post-discharge healthcare seeking. CONCLUSIONS: Ugandan mothers can collaborate in the medical care of their hospitalised infant. By performing tasks identified as important for infant care, mothers felt more prepared to care for their infant at discharge.

Zinc for infection prevention in children with sickle cell anemia: a randomized double-blind placebo-controlled trial.

Data from small clinical trials in the United States and India suggest zinc supplementation reduces infection in adolescents and adults with sickle cell anemia (SCA), but no studies of zinc supplementation for infection prevention have been conducted in children with SCA living in Africa. We conducted a randomized double-blind placebo-controlled trial to assess zinc supplementation for prevention of severe or invasive infections in Ugandan children 1.00-4.99 years with SCA. Of 252 enrolled participants, 124 were assigned zinc (10 mg) and 126 assigned placebo once daily for 12 months. The primary outcome was incidence of protocol-defined severe or invasive infections. Infection incidence did not differ between treatment arms (282 vs. 270 severe or invasive infections per 100 person-years, respectively, incidence rate ratio of 1.04 [95% confidence interval (CI), 0.81, 1.32, p=0.78]), adjusting for hydroxyurea treatment. There was also no difference between treatment arms in incidence of serious adverse events or SCA-related events. Children receiving zinc had increased serum levels after 12-months, but at study exit, 41% remained zinc deficient (<65 µg/dL). In post-hoc analysis, occurrence of stroke or death was lower in the zinc treatment arm (adjusted hazard ratio (95% CI), 0.22 (0.05, 1.00); p=0.05). Daily 10 mg zinc supplementation for 12 months did not prevent severe or invasive infections in Ugandan children with SCA, but many supplemented children remained zinc deficient. Optimal zinc dosing and the role of zinc in preventing stroke or death in SCA warrant further investigation. This trial was registered at clinicaltrials.gov as #NCT03528434.

Repeatability of Pulse Oximetry Measurements in Children During Triage in 2 Ugandan Hospitals.

BACKGROUND: In low- and middle-income countries, health workers use pulse oximeters for intermittent spot measurements of oxygen saturation (SpO2). However, the accuracy and reliability of pulse oximeters for spot measurements have not been determined. We evaluated the repeatability of spot measurements and the ideal observation time to guide recommendations during spot check measurements. METHODS: Two 1-minute measurements were taken for the 3,903 subjects enrolled in the study conducted April 2020-January 2022 in Uganda, collecting 1 Hz SpO2 and signal quality index (SQI) data. The repeatability between the 2 measurements was assessed using an intraclass correlation coefficient (ICC), calculated using a median of all seconds of non-zero SpO2 values for each recording (any quality, Q1) and again with a quality filter only using seconds with SQI 90% or higher (good quality, Q2). The ICC was also recalculated for both conditions of Q1 and Q2 using the initial 5 seconds, then the initial 10 seconds, and continuing with 5-second increments up to the full 60 seconds. Lastly, the whole minute ICC was calculated with good quality (Q2), including only records where both measurements had a mean SQI of more than 70% (Q3). RESULTS: The repeatability ICC with condition Q1 was 0.591 (95% confidence interval [CI]=0.570, 0.611). Using only the first 5 seconds of each measurement reduced the repeatability to 0.200 (95% CI=0.169, 0.230). Filtering with Q2, the whole-minute ICC was 0.855 (95% CI=0.847, 0.864). The ICC did not improve beyond the first 35 seconds. For Q3, the repeatability rose to 0.908 (95% CI=0.901, 0.914). CONCLUSIONS: Training guidelines must emphasize the importance of signal quality and duration of measurement, targeting a minimum of 35 seconds of adequate-quality, stable data. In addition, the design of new devices should incorporate user prompts and force quality checks to encourage more accurate pulse oximetry measurements.

Mortality after hospital discharge among children younger than 5 years admitted with suspected sepsis in Uganda: a prospective, multisite, observational cohort study.

BACKGROUND: Substantial mortality occurs after hospital discharge in children younger than 5 years with suspected sepsis, especially in low-income countries. A better understanding of its epidemiology is needed for effective interventions to reduce child mortality in these countries. We evaluated risk factors for death after discharge in children admitted to hospital for suspected sepsis in Uganda, and assessed how these differed by age, time of death, and location of death. METHODS: In this prospective, multisite, observational cohort study, we recruited and consecutively enrolled children aged 0-60 months admitted with suspected sepsis from the community to the paediatric wards of six Ugandan hospitals. Suspected sepsis was defined as the need for admission due to a suspected or proven infectious illness. At admission, trained study nurses systematically collected data on clinical variables, sociodemographic variables, and baseline characteristics with encrypted study tablets. Participants were followed up for 6 months after discharge by field officers who contacted caregivers at 2 months and 4 months after discharge by telephone and at 6 months after discharge in person to measure vital status, health-care seeking after discharge, and readmission details. We assessed 6-month mortality after hospital discharge among those discharged alive, with verbal autopsies conducted for children who had died after hospital discharge. FINDINGS: Between July 13, 2017, and March 30, 2020, 16 991 children were screened for eligibility. 6545 children (2927 [44·72%] female children and 3618 [55·28%] male children) were enrolled and 6191 were discharged from hospital alive. 6073 children (2687 [44·2%] female children and 3386 [55·8%] male children) completed follow-up. 366 children died in the 6-month period after discharge (weighted mortality rate 5·5%). Median time from discharge to death was 28 days (IQR 9-74). For the 360 children for whom location of death was documented, deaths occurred at home (162 [45·0%]), in transit to care (66 [18·3%]), or in hospital (132 [36·7%]) during a subsequent readmission. Death after hospital discharge was strongly associated with weight-for-age Z scores less than -3 (adjusted risk ratio [aRR] 4·7, 95% CI 3·7-5·8 vs a Z score of >-2), discharge or referral to a higher level of care (7·3, 5·6-9·5), and unplanned discharge (3·2, 2·5-4·0). Hazard ratios (HRs) for severe anaemia (<7g/dL) increased with time since discharge, from 1·7 (95% CI 0·9-3·0) for death occurring in the first time tertile to 5·2 (3·1-8·5) in the third time tertile. HRs for some discharge vulnerabilities decreased significantly with increasing time since discharge, including unplanned discharge (from 4.5 [2·9-6·9] in the first tertile to 2·0 [1·3-3·2] in the third tertile) and poor feeding status (from 7·7 [5·4-11·0] to 1·84 [1·0-3·3]). Age interacted with several variables, including reduced weight-for-age Z score, severe anaemia, and reduced admission temperature. INTERPRETATION: Paediatric mortality following hospital discharge after suspected sepsis is common, with diminishing, although persistent, risk during the first 6 months after discharge. Efforts to improve outcomes after hospital discharge are crucial to achieving Sustainable Development Goal 3.2 (ending preventable childhood deaths under age 5 years). FUNDING: Grand Challenges Canada, Thrasher Research Fund, BC Children's Hospital Foundation, and Mining4Life.

Parental participation in the care of hospitalized neonates in low- and middle-income countries: A systematic review and meta-analysis.

Introduction: To determine the effect of parental participation in hospital care on neonatal and parental outcomes in low- and middle-income countries (LMICs) and to identify the range of parental duties in the care of hospitalized neonates in LMICs. Methods: We searched CINAHL, CENTRAL, LILACs, MEDLINE, EMBASE and Web of Science from inception to February 2022. Randomized and non-randomized studies from LMICs were eligible if parents performed one or more roles traditionally undertaken by healthcare staff. The primary outcome was hospital length-of-stay. Secondary outcomes included mortality, readmission, breastfeeding, growth, development and parental well-being. Data was extracted in duplicate by two independent reviewers using a piloted extraction form. Results: Eighteen studies (eight randomized and ten non-randomized) were included from seven middle-income countries. The types of parental participation included hygiene and infection prevention, feeding, monitoring and documentation, respiratory care, developmental care, medication administration and decision making. Meta-analyses showed that parental participation was not associated with hospital length-of-stay (MD -2.35, 95% CI -6.78-2.07). However, parental involvement was associated with decreased mortality (OR 0.46, 95% CI 0.22-0.95), increased breastfeeding (OR 2.97 95% CI 1.65-5.35) and decreased hospital readmission (OR 0.36, 95% CI 0.16-0.81). Narrative synthesis demonstrated additional benefits for growth, short-term neurodevelopment and parental well-being. Ten of the eighteen studies had a high risk of bias. Conclusion: Parental participation in neonatal hospital care is associated with improvement in several key neonatal outcomes in middle-income countries. The lack of data from low-income countries suggests that there remains barriers to parental participation in resource-poor settings. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=187562], identifier [CRD42020187562].

A proposed de-identification framework for a cohort of children presenting at a health facility in Uganda.

Data sharing has enormous potential to accelerate and improve the accuracy of research, strengthen collaborations, and restore trust in the clinical research enterprise. Nevertheless, there remains reluctancy to openly share raw data sets, in part due to concerns regarding research participant confidentiality and privacy. Statistical data de-identification is an approach that can be used to preserve privacy and facilitate open data sharing. We have proposed a standardized framework for the de-identification of data generated from cohort studies in children in a low-and-middle income country. We applied a standardized de-identification framework to a data sets comprised of 241 health related variables collected from a cohort of 1750 children with acute infections from Jinja Regional Referral Hospital in Eastern Uganda. Variables were labeled as direct and quasi-identifiers based on conditions of replicability, distinguishability, and knowability with consensus from two independent evaluators. Direct identifiers were removed from the data sets, while a statistical risk-based de-identification approach using the k-anonymity model was applied to quasi-identifiers. Qualitative assessment of the level of privacy invasion associated with data set disclosure was used to determine an acceptable re-identification risk threshold, and corresponding k-anonymity requirement. A de-identification model using generalization, followed by suppression was applied using a logical stepwise approach to achieve k-anonymity. The utility of the de-identified data was demonstrated using a typical clinical regression example. The de-identified data sets was published on the Pediatric Sepsis Data CoLaboratory Dataverse which provides moderated data access. Researchers are faced with many challenges when providing access to clinical data. We provide a standardized de-identification framework that can be adapted and refined based on specific context and risks. This process will be combined with moderated access to foster coordination and collaboration in the clinical research community.

Smart triage: Development of a rapid pediatric triage algorithm for use in low-and-middle income countries.

Introduction: Early and accurate recognition of children at risk of progressing to critical illness could contribute to improved patient outcomes and resource allocation. In resource limited settings digital triage tools can support decision making and improve healthcare delivery. We developed a model for rapid identification of critically ill children at triage. Methods: This was a prospective cohort study of acutely ill children presenting at Jinja Regional Referral Hospital in Eastern Uganda. Variables collected in the emergency department informed the development of a logistic model based on hospital admission using bootstrap stepwise regression. Low and high-risk thresholds for 90% minimum sensitivity and specificity, respectively generated three risk level categories. Performance was assessed using receiver operating characteristic curve analysis on a held-out test set generated by an 80:20 split with 10-fold cross validation. A risk stratification table informed clinical interpretation. Results: The model derivation cohort included 1,612 participants, with an admission rate of approximately 23%. The majority of admitted patients were under five years old and presenting with sepsis, malaria, or pneumonia. A 9-predictor triage model was derived: logit (p) = -32.888 + (0.252, square root of age) + (0.016, heart rate) + (0.819, temperature) + (-0.022, mid-upper arm circumference) + (0.048 transformed oxygen saturation) + (1.793, parent concern) + (1.012, difficulty breathing) + (1.814, oedema) + (1.506, pallor). The model afforded good discrimination, calibration, and risk stratification at the selected thresholds of 8% and 40%. Conclusion: In a low income, pediatric population, we developed a nine variable triage model with high sensitivity and specificity to predict who should be admitted. The triage model can be integrated into any digital platform and used with minimal training to guide rapid identification of critically ill children at first contact. External validation and clinical implementation are in progress.

Institutionalizing a Regional Model for Improving Quality of Newborn Care at Birth Across Hospitals in Eastern Uganda: A 4-Year Story.

INTRODUCTION: Despite the rapid increase in facility deliveries in Uganda, the number of adverse birth outcomes (e.g., neonatal and maternal deaths) has remained high. We aimed to codesign and co-implement a locally designed package of interventions to improve the quality of care in hospitals in the Busoga region. DESIGN AND IMPLEMENTATION: This project was designed and implemented in 3 phases in the 6 main hospitals in east-central Uganda from 2013 to 2016. First, the inception phase engaged health system managers to codesign the intervention. Second, the implementation phase involved training health providers, strengthening the data information system, and providing catalytic equipment and medicines to establish newborn care units (NCUs) within the existing infrastructure. Third, the hospital collaborative phase focused on clinical mentorship, maternal and perinatal death reviews (MPDRs), and collaborative learning sessions. ACHIEVEMENTS: In all 6 participating hospitals, we achieved institutionalization of NCUs in maternity units by establishing kangaroo mother care areas, resuscitation corners, and routine MPDRs. These improvements were associated with reduced maternal and neonatal deaths. Facilitators of success included a simple, low-cost, and integrated package designed with local health managers; the emergence of local neonatal care champions; implementation and support over a reasonably long period; decentralization of newborn care services; and use of mainly existing local resources (e.g., physical space, human resources, and commodities). Barriers to success related to limited hospital resources, unstable electricity, and limited participation from doctors. More advanced NCUs have been established in 3 of the 6 hospitals, and 7 high-volume comprehensive health centers have been established with functional NCUs. CONCLUSION: The involvement of local health workers and leaders was the foundation for designing, sustaining, and scaling up feasible interventions by harnessing available resources. These findings are relevant for the quality of care improvement efforts in Uganda and other resource-restrained settings.