Andrew Ndamira

Pediatric sepsis in the developing world: challenges in defining sepsis and issues in post-discharge mortality.

Sepsis represents the progressive underlying inflammatory pathway secondary to any infectious illness, and ultimately is responsible for most infectious disease-related deaths. Addressing issues related to sepsis has been recognized as an important step towards reducing morbidity and mortality in developing countries, where the majority of the 7.5 million annual deaths in children under 5 years of age are considered to be secondary to sepsis. However, despite its prevalence, sepsis is largely neglected. Application of sepsis definitions created for use in resource-rich countries are neither practical nor feasible in most developing country settings, and alternative definitions designed for use in these settings need to be established. It has also been recognized that the inflammatory state created by sepsis increases the risk of post-discharge morbidity and mortality in developed countries, but exploration of this issue in developing countries is lacking. Research is urgently required to characterize better this potentially important issue.

Pediatric Post-Discharge Mortality in Resource Poor Countries: A Systematic Review

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

Postdischarge mortality in children with acute infectious diseases: derivation of postdischarge mortality prediction models.

Objectives To derive a model of paediatric postdischarge mortality following acute infectious illness. Design Prospective cohort study. Setting 2 hospitals in South-western Uganda. Participants 1307 children of 6 months to 5 years of age were admitted with a proven or suspected infection. 1242 children were discharged alive and followed up 6 months following discharge. The 6-month follow-up rate was 98.3%. Interventions None. Primary and secondary outcome measures The primary outcome was postdischarge mortality within 6 months following the initial hospital discharge. Results 64 children died during admission (5.0%) and 61 died within 6 months of discharge (4.9%). Of those who died following discharge, 31 (51%) occurred within the first 30 days. The final adjusted model for the prediction of postdischarge mortality included the variables mid-upper arm circumference (OR 0.95, 95% CI 0.94 to 0.97, per 1 mm increase), time since last hospitalisation (OR 0.76, 95% CI 0.61 to 0.93, for each increased period of no hospitalisation), oxygen saturation (OR 0.96, 95% CI 0.93 to 0·99, per 1% increase), abnormal Blantyre Coma Scale score (OR 2.39, 95% CI 1·18 to 4.83), and HIV-positive status (OR 2.98, 95% CI 1.36 to 6.53). This model produced a receiver operating characteristic curve with an area under the curve of 0.82. With sensitivity of 80%, our model had a specificity of 66%. Approximately 35% of children would be identified as high risk (11.1% mortality risk) and the remaining would be classified as low risk (1.4% mortality risk), in a similar cohort. Conclusions Mortality following discharge is a poorly recognised contributor to child mortality. Identification of at-risk children is critical in developing postdischarge interventions. A simple prediction tool that uses 5 easily collected variables can be used to identify children at high risk of death after discharge. Improved discharge planning and care could be provided for high-risk children.

Application of Sepsis Definitions to Pediatric Patients Admitted With Suspected Infections in Uganda.

Objectives: 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. Design: 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. Setting: The pediatric ward of two hospitals in Mbarara, Uganda. Patients: Admitted children between 6 months and 5 years with a confirmed or suspected infection. Interventions: None. Measurements and Main Results: 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. Conclusions: 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.

The PAediatric Risk Assessment (PARA) Mobile App to Reduce Postdischarge Child Mortality: Design, Usability, and Feasibility for Health Care Workers in Uganda

Background Postdischarge death in children is increasingly being recognized as a major contributor to overall child mortality. The PAediatric Risk Assessment (PARA) app is an mHealth tool developed to aid health care workers in resource-limited settings such as Sub-Saharan Africa to identify pediatric patients at high risk of both in-hospital and postdischarge mortality. The intended users of the PARA app are health care workers (ie, nurses, doctors, and clinical officers) with varying levels of education and technological exposure, making testing of this clinical tool critical to successful implementation. Objective Our aim was to summarize the usability evaluation of the PARA app among target users, which consists of assessing the ease of use, functionality, and navigation of the interfaces and then iteratively improving the design of this clinical tool. Methods Health care workers (N=30) were recruited to participate at Mbarara Regional Referral Hospital and Holy Innocents Children’s Hospital in Mbarara, Southwestern Uganda. This usability study was conducted in two phases to allow for iterative improvement and testing of the interfaces. The PARA app was evaluated using quantitative and qualitative measures, which were compared between Phases 1 and 2 of the study. Participants were given two patient scenarios that listed hypothetical information (ie, demographic, social, and clinical data) to be entered into the app and to determine the patient’s risk of in-hospital and postdischarge mortality. Time-to-completion and user errors were recorded for each participant while using the app. A modified computer system usability questionnaire was utilized at the end of each session to elicit user satisfaction with the PARA app and obtain suggestions for future improvements. Results The average time to complete the PARA app decreased by 30% from Phase 1 to Phase 2, following user feedback and modifications. Participants spent the longest amount of time on the oxygen saturation interface, but modifications following Phase 1 cut this time by half. The average time-to-completion (during Phase 2) for doctors/medical students was 3 minutes 56 seconds. All participants agreed they would use the PARA app if available at their health facility. Given a high PARA risk score, participants suggested several interventions that would be appropriate for the sociocultural context in southwestern Uganda, which involved strengthening discharge and referral procedures within the current health care system. Conclusions Through feedback and modifications made during this usability study, the PARA app was developed into a user-friendly app, encompassing user expectations and culturally intuitive interfaces for users with a range of technological exposure. Doctors and medical students had shorter task completion times, though all participants reported the usefulness of this tool to improve postdischarge outcomes.

Scheduled Follow-Up Referrals and Simple Prevention Kits Including Counseling to Improve Post-Discharge Outcomes Among Children in Uganda: A Proof-of-Concept Study

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. 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. ABSTRACT 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.

Clinical features and survival among children with retinoblastoma in Uganda

Aims To characterise the clinical features, treatment and outcome of children diagnosed with retinoblastoma in Uganda. Methods The study comprised a 6-year nationwide enrolment with follow-up. Results In total, 282 cases were enrolled, 26% (72) were bilateral; 6% were lost to follow-up. Almost all diagnoses in the first affected eye were International Classification of Retinoblastoma group E or worse. Histology was available for 92%; of those, 45%, had extraocular tumour at diagnosis. Enucleation of the first eye was done for 271; 94 received radiotherapy to the socket and in the last 2 years, 70 children received chemotherapy. At close of study, 139 children had died. Survival, as determined in a proportional hazards model adjusted for age, sex, laterality and treatment era (pre or post introduction of chemotherapy), varied by extent of the tumour (p<0.001); children with only intraocular involvement were 80% less likely to die (HR=0.21, 95% CI 0.12 to 0.35) compared with children with extraocular involvement. Conclusions Diagnostic delay results in relatively high mortality among children with retinoblastoma in Uganda. There is an urgent need for more effective treatment modalities, particularly chemotherapy, and nationwide efforts to encourage earlier access to medical care.

Pediatric in-Hospital Death from Infectious Disease in Uganda: Derivation of Clinical Prediction Models.

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

Selecting candidate predictor variables for the modelling of post-discharge mortality from sepsis: a protocol development project

BACKGROUND Post-discharge mortality is a frequent but poorly recognized contributor to child mortality in resource limited countries. The identification of children at high risk for post-discharge mortality is a critically important first step in addressing this problem. OBJECTIVES The objective of this project was to determine the variables most likely to be associated with post-discharge mortality which are to be included in a prediction modelling study. METHODS A two-round modified Delphi process was completed for the review of a priori selected variables and selection of new variables. Variables were evaluated on relevance according to (1) prediction (2) availability (3) cost and (4) time required for measurement. Participants included experts in a variety of relevant fields. RESULTS During the first round of the modified Delphi process, 23 experts evaluated 17 variables. Forty further variables were suggested and were reviewed during the second round by 12 experts. During the second round 16 additional variables were evaluated. Thirty unique variables were compiled for use in the prediction modelling study. CONCLUSION A systematic approach was utilized to generate an optimal list of candidate predictor variables for the incorporation into a study on prediction of pediatric post-discharge mortality in a resource poor setting.

Improving survival of retinoblastoma in Uganda

Background Diagnostic delay results in relatively high mortality among children with retinoblastoma in Uganda, where treatment was limited to surgery and, for some, radiotherapy. In order to improve outcomes, a simple programme of neoadjuvant and adjuvant chemotherapy was introduced. Here we report survival before and after this change to medical practice. Methods Affordable standard off-patent chemotherapy agents were administered by trained paramedical staff to groups of patients at the same time. Survival before and after the introduction of chemotherapy was monitored. Between 2006 and 2013 a total of 270 patients with retinoblastoma were included, 181 treated prior to chemotherapy and 89 after (beginning in 2009). We had 94% follow-up and 249 had histological verification of diagnosis. Results Using a proportional hazards model adjusted for age, sex and laterality, children treated after chemotherapy was introduced had a 37% lower risk of dying (HR 0.63, 95% CI 0.41 to 0.99) compared with children treated before. Prior to the introduction of chemotherapy only 15% of children who survived bilateral disease retained vision after treatment compared with 71% after chemotherapy. Conclusions The introduction of chemotherapy proved safe and cost-effective in non-specialist hands and was associated with significant improvements in survival and, among bilateral cases, in preserving vision.