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.

Transitions from hospital to home: A mixed methods study to evaluate pediatric discharges in Uganda.

The World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) guidelines recognize the importance of discharge planning to ensure continuation of care at home and appropriate follow-up. However, insufficient attention has been paid to post discharge planning in many hospitals contributing to poor implementation. To understand the reasons for suboptimal discharge, we evaluated the pediatric discharge process from hospital admission through the transition to care within the community in Ugandan hospitals. This mixed methods prospective study enrolled 92 study participants in three phases: patient journey mapping for 32 admitted children under-5 years of age with suspected or proven infection, discharge process mapping with 24 pediatric healthcare workers, and focus group discussions with 36 primary caregivers and fathers of discharged children. Data were descriptively and thematically analyzed. We found that the typical discharge process is often not centered around the needs of the child and family. Discharge planning often does not begin until immediately prior to discharge and generally does not include caregiver input. Discharge education and counselling are generally limited, rarely involves the father, and does not focus significantly on post-discharge care or follow-up. Delays in the discharge process itself occur at multiple points, including while awaiting a physical discharge order and then following a discharge order, mainly with billing or transportation issues. Poor peri-discharge care is a significant barrier to optimizing health outcomes among children in Uganda. Process improvements including initiation of early discharge planning, improved communication between healthcare workers and caregivers, as well as an increased focus on post-discharge care, are key to ensuring safe transitions from facility-based care to home-based care among children recovering from severe illness.

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).

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.

Prognostic algorithms for post-discharge readmission and mortality among mother-infant dyads: an observational study protocol.

Introduction: In low-income country settings, the first six weeks after birth remain a critical period of vulnerability for both mother and newborn. Despite recommendations for routine follow-up after delivery and facility discharge, few mothers and newborns receive guideline recommended care during this period. Prediction modelling of post-delivery outcomes has the potential to improve outcomes for both mother and newborn by identifying high-risk dyads, improving risk communication, and informing a patient-centered approach to postnatal care interventions. This study aims to derive post-discharge risk prediction algorithms that identify mother-newborn dyads who are at risk of re-admission or death in the first six weeks after delivery at a health facility. Methods: This prospective observational study will enroll 7,000 mother-newborn dyads from two regional referral hospitals in southwestern and eastern Uganda. Women and adolescent girls aged 12 and above delivering singletons and twins at the study hospitals will be eligible to participate. Candidate predictor variables will be collected prospectively by research nurses. Outcomes will be captured six weeks following delivery through a follow-up phone call, or an in-person visit if not reachable by phone. Two separate sets of prediction models will be built, one set of models for newborn outcomes and one set for maternal outcomes. Derivation of models will be based on optimization of the area under the receiver operator curve (AUROC) and specificity using an elastic net regression modelling approach. Internal validation will be conducted using 10-fold cross-validation. Our focus will be on the development of parsimonious models (5-10 predictor variables) with high sensitivity (>80%). AUROC, sensitivity, and specificity will be reported for each model, along with positive and negative predictive values. Discussion: The current recommendations for routine postnatal care are largely absent of benefit to most mothers and newborns due to poor adherence. Data-driven improvements to postnatal care can facilitate a more patient-centered approach to such care. Increasing digitization of facility care across low-income settings can further facilitate the integration of prediction algorithms as decision support tools for routine care, leading to improved quality and efficiency. Such strategies are urgently required to improve newborn and maternal postnatal outcomes. Clinical trial registration: https://clinicaltrials.gov/, identifier (NCT05730387).

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.

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.

Cost-effectiveness analysis protocol of the Smart Triage program: A point-of-care digital triage platform for pediatric sepsis in Eastern Uganda.

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.

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.