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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.

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.

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: Clinical trials to reduce household air pollution have largely focused on cookstoves and have been in part limited by suboptimal adoption of cleaner cooking technologies. Less is known about the adoption and perceptions of clean lighting interventions. Methods: As part of a randomized controlled trial of indoor solar lighting systems (ClinicalTrials.gov NCT03351504), we conducted a mixed methods study to identify contextual factors determining uptake and perception of the solar lighting intervention. Sensors were incorporated into the intervention solar lighting system to measure uptake and use over time. Health-related quality of life was measured with the EQ-5D-5L. Qualitative interviews were conducted with all trial participants. Findings: Uptake of the intervention solar lighting system was high with daily use averaging 8·23 ± 5·30 hours per day. In mixed effects regression models, the intervention solar lighting system increased the EQ5D index by 0·083 [0·024 - 0·141], p = 0·006. Qualitative data suggest that solar lighting was associated with numerous benefits to study participants, including improved household finances, improved educational performance of children, increased household safety, improved family and community cohesion, and improved perceived household health. Interpretation: Uptake of the solar lighting intervention was high and led to improved health-related quality of life. The solar lighting intervention was a transformative household energy technology which improve multiple domains of the Social Determinants of Health (SDOH). Trials focused only on traditional health outcomes may underestimate the overall value of clean household energy interventions to the end user. Trial Registration: ClinicalTrials.gov NCT03351504 Funding Statement: US National Institutes of Health, Harvard School of Public Health, American Thoracic Society, Massachusetts General Hospital Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was approved by the Mbarara University of Science and Technology (Protocol #02/11-16) and the Partners Human Research Committee (Protocol 2017P000306/PHS), the Ugandan National Council of Science and Technology (Protocol #PS 42) and the Ugandan President’s office.

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.

According to the WHO, 15,000 children under five years are dying every day from preventable causes with 80% of these children being born in low-income countries. Portable optical medical diagnostic devices can help physicians, nurses and untrained health workers to objectively identify children who are at a higher risk of dying. In the last 2 years, we collected the oxygenation values of the brachioradialis muscle, using a commercial Near Infrared Spectroscopy (NIRS) device, in 200 children under 5 years admitted in two hospitals in Uganda. Data revealed that the tissue oxygen saturation decrease during a vascular occlusion predicts children at higher risk better than other vital signs (SpO2, respiration rate, heart rate and temperature). Based on these results, we designed a low cost Continuous Wave Spatially Resolved NIRS device controlled by a smartphone in order to extend our study to a larger population and confirm our observation. The total cost of this device (excluding the smartphone) is less than $100. The preliminary tests suggest a significant potential of our low cost mobile NIRS device and oxygenation values closely matching those reported by the best device on the market.

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.

Supplemental Digital Content is available in the text., Objectives: Sepsis is responsible for a substantial proportion of global childhood morbidity and mortality. However, evidence demonstrates major inaccuracies in the use of the term “sepsis” in clinical practice, coding, and research. Current and previous definitions of sepsis have been developed using expert consensus but the specific criteria used to identify children with sepsis have not been rigorously evaluated. Therefore, as part of the Society of Critical Care Medicine’s Pediatric Sepsis Definition Taskforce, we will conduct a systematic review to synthesize evidence on individual factors, clinical criteria, or illness severity scores that may be used to identify children with infection who have or are at high risk of developing sepsis-associated organ dysfunction and separately those factors, criteria, and scores that may be used to identify children with sepsis who are at high risk of progressing to multiple organ dysfunction or death. Data Sources: We will identify eligible studies by searching the following databases: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Study Selection: We will include all randomized trials and cohort studies published between January 1, 2004, and March 16, 2020. Data Extraction: Data extraction will include information related to study characteristics, population characteristics, clinical criteria, and outcomes. Data Synthesis: We will calculate sensitivity and specificity of each criterion for predicting sepsis and conduct a meta-analysis if the data allow. We will also provide pooled estimates of overall hospital mortality. Conclusions: The potential risk factors, clinical criteria, and illness severity scores from this review which identify patients with infection who are at high risk of developing sepsis-associated organ dysfunction and/or progressing to multiple organ dysfunction or death will be used to inform the next steps of the Pediatric Sepsis Definition Taskforce.

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.

More people have mobile phones in Africa than at any point in history. Mobile health (m-health), the use of mobile phones to support the delivery of health services, has expanded in recent years. Several models have been proposed for conceptualizing m-health in the fields of maternal-child health and chronic diseases. We conducted a literature review of m-health interventions for HIV prevention and care in African countries and present the findings in the context of a simplified framework.; Our review identified applications of m-health for HIV prevention and care categorized by the following three themes: patient-care focused applications, such as health behavior change, health system-focused applications, such as reporting and data collection, and population health-focused applications, including HIV awareness and testing campaigns.; The potential for m-health in Africa is numerous and should not be limited only to direct patient-care focused applications. Although the use of smart phone technology is on the rise in Africa, text messaging remains the primary mode of delivering m-health interventions. The rate at which mobile phone technologies are being adopted may outpace the rate of evaluation. Other methods of evaluation should be considered beyond only randomized-controlled trials.

Study objective Corticosteroids (steroids) are often used to mitigate symptoms and prevent subsequent reactions in emergency department (ED) patients with allergic reactions, despite a lack of evidence to support their use. We sought to determine the association of steroid administration with improved clinical outcomes. Methods Adult allergy-related encounters to 2 urban EDs during a 5-year period were identified and classified as "anaphylaxis" or "allergic reaction." Regional and provincial databases identified subsequent ED visits or deaths within a 7-day period. The primary outcome was allergy-related ED revisits in the steroid- and nonsteroid-exposed groups, adjusting for potential confounders with a propensity score analysis; secondary outcomes included the number of clinically important biphasic reactions and deaths. Results Two thousand seven hundred one encounters (473 anaphylactic) were included; 48% were treated with steroids. Allergy-related ED revisits occurred in 5.8% and 6.7% of patients treated with and without steroids, respectively (adjusted odds ratio [OR] 0.91; 95% confidence interval [CI] 0.64 to 1.28), with a number needed to treat (NNT) to benefit of 176 (95% CI NNT to benefit 39 to ∞ to NNT to harm 65). The adjusted OR in the anaphylaxis subgroup was 1.12 (95% CI 0.41 to 3.27). In the allergic reaction group, the adjusted OR was 0.91 (95% CI 0.63 to 1.31), with an NNT to benefit of 173 (95% CI NNT to benefit 38 to ∞ to NNT to harm 58). In the steroid and nonsteroid groups, there were 4 and 1 clinically important biphasic reactions, respectively. There were no deaths. Conclusion Among ED patients with allergic reactions or anaphylaxis, corticosteroid use was not associated with decreased relapses to additional care within 7 days.

Background There is a need to critically appraise clinical practice guidelines in order to ensure safe and effective practices are being implemented to optimize patient care. Appraising guidelines within one therapeutic area enable recommendations for improvement during guideline creation and dissemination. Objectives Study objectives were to systematically appraise selected published guidelines used in the treatment of pediatric infectious diseases and to make recommendations for improvement throughout the development and dissemination processes. Setting The study occurred between collaborative academic and practice-based institutions located in Canada and Qatar. Methods A literature search identified guidelines for management of pediatric infectious diseases from 1997 to 2013. Each guideline was appraised by four independent assessors, according to the appraisal of guidelines for research and evaluation II (AGREE II) instrument. Standardized domain scores were calculated for each guideline and pooled. Final endorsements for use in clinical practice were also determined. Inter-rater reliability was assessed using intraclass correlation coefficients. Main outcome measure Standardized domain scores according to the AGREE II instrument. Results Twenty guidelines met inclusion criteria and were appraised. Pooled domain scores were: scope and purpose (69.9), stakeholder involvement (40.1), rigour of development (47.1), clarity of presentation (73.4), applicability (23.7), editorial independence (46.7), and overall assessment (55.8). Two (10 %) guidelines were recommended for use without revision, 13 (65 %) guidelines were recommended with modifications, and 5 (25 %) guidelines were not recommended for implementation into practice. Inter-rater reliability was moderate to good with intra-class correlations of 0.65–0.93 per guideline. Conclusion The majority of appraised guidelines were moderately rated, with a 25 % of guidelines not recommended for use. Strategies for improvement require the involvement of all key stakeholders (caregivers, patients, and allied health professionals), and consideration of facilitators, barriers and resource implications during implementation. Additionally, critical appraisal of guidelines should become standard practice prior to adoption into clinical settings.

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

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. Keywords: Candidate predictor variables, pediatrics, prediction, post-discharge mortality, sepsis

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. [JMIR Mhealth Uhealth 2016;4(1):e16]

ACADEMIC EMERGENCY MEDICINE 2012; 19:640–649 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: Adverse drug events (ADEs) are unintended and harmful consequences of medication use. They are associated with high health resource use and cost. Yet, high levels of inaccuracy exist in their identification in clinical practice, with over one-third remaining unidentified in the emergency department (ED). The study objective was to derive clinical decision rules (CDRs) that are sensitive for the detection of ADEs, allowing their systematic identification early in a patient’s hospital course. Methods: This was a prospective observational cohort study carried out in two Canadian tertiary care hospitals. Participants were adults presenting to the ED having ingested at least one prescription or over-the-counter medication within 2 weeks. Nurses and physicians evaluated patients for standardized clinical findings. A second evaluator performed interobserver assessments of predictor variables in a subset of patients. Pharmacists, who were blinded to the predictor variables, evaluated all patients for ADEs. An independent committee reviewed and adjudicated cases where the ADE assessment was uncertain or the pharmacist’s diagnosis differed from the physician’s working diagnosis. The primary outcome was an ADE that required a change in medical therapy, diagnostic testing, consultation, or hospital admission. CDRs were derived using kappa coefficients, chi-square statistics, and recursive partitioning. Results: Among 1,591 patients, 131 (8.2%, 95% confidence interval [CI] = 7.0% to 9.7%) were diagnosed with the primary outcome. The following variables were associated with ADEs and were used to derive two CDRs: 1) presence of comorbid conditions, 2) antibiotic use within 7 days, 3) medication changes within 28 days, 4) age ≥80 years, 5) arrival by ambulance, 6) triage acuity, 7) recent hospital admission, 8) renal failure, and 9) use of three or more prescription medications. The more sensitive rule had a sensitivity of 96.7% (95% CI = 91.8% to 98.6%) and required 40.8% (95% CI = 37.7% to 42.9%) of patients to have medication review. The more specific rule had a sensitivity 90.8% (95% CI = 81.4% to 95.7%) and required 28.3% of patients to proceed to medication review. Conclusions: The authors derived CDRs that identified patients with ADEs with high sensitivity. These rules may improve the identification of ADEs early in a patient’s hospital course while limiting the number of patients requiring a detailed medication review.

OBJECTIVES: Diabetes is increasing in prevalence across Canada. In the continuously evolving primary care landscape, practitioners from varied training paths are claiming rights to care for patients, including those with diabetes. Little is known about patient exposure to complementary and alternative medicine (CAM) providers, or about such providers' use of guideline-based monitoring and treatment recommendations. The purpose of this study was to examine compliance with 4 recommendations (influenza vaccination, eye examination, glycated hemoglobin measurement and foot exam) by patients with diabetes who use CAM providers compared to those who exclusively use primary care physicians. METHODS: We analyzed data on 7209 patients with diabetes using the Canadian Community Health Survey. Patients with exposure to CAM providers were compared with individuals who were exposed to a family physician only. Multivariate logistic regression was conducted adjusted for age, sex, duration of diabetes, insulin/oral antihyperglycemic agent use and education. RESULTS: Approximately 4% of persons had been exposed to CAM providers in the preceding year. The odds ratio for receiving influenza vaccination among those exposed to a CAM provider was 0.94 (95% CI 0.74–1.17). The odds ratios for eye examinations in the preceding 24 months, and for foot examinations and glycated hemoglobin tests in the preceding 12 months were 1.02 (95% CI 0.69–1.48), 1.18 (0.83–1.67) and 1.09 (95% CI 0.71–1.66), respectively. CONCLUSION: Our results did not show statistical significance in any of the 4 outcomes analyzed. This study supports others suggesting that persons using CAM providers do so to complement traditional medical care, rather than as an alternative to such care.

Objective Anaemia affects the majority of children in sub-Saharan Africa (SSA). Previous studies of risk factors for anaemia have been limited by sample size, geography and the association of many risk factors with poverty. In order to measure the relative impact of individual, maternal and household risk factors for anaemia in young children, we analysed data from all SSA countries that performed haemoglobin (Hb) testing in the Demographic and Health Surveys. Design and setting This cross-sectional study pooled household-level data from the most recent Demographic and Health Surveys conducted in 27 SSA between 2008 and 2014. Participants 96 804 children age 6–59 months. Results The prevalence of childhood anaemia (defined as Hb

Medication-related visits to the emergency department are an important but poorly understood phenomenon. We sought to evaluate the frequency, severity and preventability of drug-related visits to the emergency department.We performed a prospective observational study of randomly selected adults presenting to the emergency department over a 12-week period. Emergency department visits were identified as drug-related on the basis of assessment by a pharmacist research assistant and an emergency physician; discrepancies were adjudicated by 2 independent reviewers.Among the 1017 patients included in the study, the emergency department visit was identified as drug-related for 122 patients (12.0%, 95% confidence interval [CI] 10.1%-14.2%); of these, 83 visits (68.0%, 95% CI 59.0%-76.2%) were deemed preventable. Severity was classified as mild in 15.6% of the 122 cases, moderate in 74.6% and severe in 9.8%. The most common reasons for drug-related visits were adverse drug reactions (39.3%), nonadherence (27.9%) and use of the wrong or suboptimal drug (11.5%). The probability of admission was significantly higher among patients who had a drug-related visit than among those whose visit was not drug-related (OR 2.18, 95% CI 1.46-3.27, p0.001), and among those admitted, the median length of stay was longer (8.0 [interquartile range 23.5] v. 5.5 [interquartile range 10.0] days, p = 0.06).More than 1 in 9 emergency department visits are due to drug-related adverse events, a potentially preventable problem in our health care system.

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

Introduction : Expanding and sustaining antiretroviral therapy (ART) coverage may require simplified HIV service delivery strategies that concomitantly reduce the burden of care on the health system and patients while ensuring optimal outcomes. We conducted a systematic review to assess the impact of reduced frequency of clinic visits and drug dispensing on patient outcomes. Methods : As part of the development process of the World Health Organization antiretroviral (ARV) guidelines, we systematically searched medical literature databases for publications up to 30 August 2016. Information was extracted on trial characteristics, patient characteristics and the following outcomes: mortality, morbidity, treatment adherence, retention, patient and provider acceptability, cost and patients exiting the programme. When feasible, conventional pairwise meta-analyses were conducted. Results and discussion : Of 6443 identified citations, 21 papers, pertaining to 16 studies, were included in this review, with 11 studies contributing to analyses. Although analyses were feasible, they were limited by the sparse evidence base, despite the importance of the research area, and relatively low quality. Comparative analyses of eight studies reporting on frequency of clinic visits showed that less frequent clinic visits led to higher odds of being retained in care (odds ratio [OR]: 1.90; 95% CI: 1.21–2.99). No differences were found with respect to viral failure, morbidity or mortality; however, most estimates were favourable to reduced clinic visits. Reduced frequency of ARVs pick-ups showed a trend towards better retention (OR: 1.93; 95% CI: 0.62–6.04). Strategies using community support tended to have better outcomes; however, their implementation varied, particularly by location. External validity may be questionable. Conclusions : Our systematic review suggests that reduction of clinical visits (and likely ARVs pick-ups) may improve clinical outcomes, and that they are a viable option to relieve health systems and reduce burden of care for PLHIV. Strategies aimed at reducing clinic visits or drug refill services should focus on stable patients who are virally suppressed, tolerant to their drug regimen and fully adherent. These strategies may be critical to the current changes taking place in HIV treatment policy; thus, due to the data limitations, further high quality research is needed to inform policy and programmatic interventions. Keywords HIV Services; clinical visit frequency; antiretroviral therapy HIV/AIDS; systematic literature review; meta-analysis To access the supplementary material to this article please see Supplementary Files under Article Tools online. (Published: 21 July 2017) Mutasa-Apollo T et al. Journal of the International AIDS Society 2017, 20 :21647 http://www.jiasociety.org/index.php/jias/article/view/21647 | http://dx.doi.org/10.7448/IAS.20.5.21647

We have designed a mobile device application (RRate), to provide an efficient measurement of respiratory rate with clinically acceptable accuracy. The method is based on analysis of multiple consecutive breath intervals. We investigated in this study the difference in measurement variability between breaths as a representative of recording quality. Respiratory rate of 322 children aged 0 - 12 years at a Ugandan rural health centre were recorded using the RRate mobile application, and compared to respiratory rate recordings obtained from 22 volunteers using the RRate application while observing 10 videos of children breathing in a lab setting. The variability of the recorded breaths (confidence) of both groups follow a similar Weibull distribution. However, we observed a trend towards higher variability in the data obtained in the field (median 89.7% confidence) compared to the data obtained in the laboratory setting (median 92.6% confidence). This suggests that it is more difficult to obtain consistent measurements when assessing patients in a clinical setting, and therefore the confidence in the measured respiratory rate is reduced. The mobile device application provided a respiratory rate value up to 6 times faster than the current practice of one minute counting. The measure of variability between individual measured breaths provided a powerful way to display confidence in a measurement.

A 28-year-old Aboriginal woman was admitted to hospital after presenting to the emergency department with a three-day history of fever, chills, difficulty swallowing because of a sore throat, and cough with production of sputum. The patient’s history included juvenile rheumatoid arthritis that was

Objectives Rhabdomyolysis, as defined by an elevation in creatine kinase (CK), may lead to hemodialysis and death in emergency department (ED) patients, but the patient characteristics, associated conditions, and 30-day outcomes of patients with CK values over 1,000 U/L have not been described. Methods All consecutive ED patients with serum CK values over 1,000 U/L between January 1, 2006, and December 31, 2008, were retrospectively identified from two urban hospitals. Patient characteristics, ED treatment, and ED discharge diagnoses were determined by medical record review. Provincial databases were linked to identify patients who died or were treated with hemodialysis within 30 days. The primary outcome was the combined occurrence of death or need for hemodialysis within 30 days. Secondary outcomes included the incidence of acute kidney injury (AKI) and the proportion of patients with initial estimated glomerular filtration rates (eGFR) > 60 mL/min/1.73 m2 who died or required hemodialysis. Results Four-hundred patients were identified, the median age was 50 years (interquartile range [IQR] = 35 to 69 years), and 77% were male, with 35% of patients discharged home from the ED. The most common ED discharge diagnoses were related to recreational drug use, infections, and traumatic or musculoskeletal complaints. Within 30 days, 32 (8.0%, 95% confidence interval [CI] = 5.3% to 11%) experienced primary outcomes, with 18 (4.5%, 95% CI = 2.55% to 6.5%) requiring hemodialysis and 21 deaths (5.3%, 95% CI = 3.1% to 7.4%). AKI occurred in 151 patients (38%, 95% CI = 33% to 43%). Of the 257 patients (64%) with initial eGFRs > 60 mL/min/1.73 m2, none required hemodialysis. Conclusions In ED patients with initial CK > 1,000 U/L, the incidence of death or hemodialysis was 8% within 30 days. Patients with initial eGFRs > 60 mL/min/1.73 m2 appear to be at a low risk of these outcomes from rhabdomyolysis. Resumen Objetivos La rabdomiolisis, definida como una elevacion de la creatina cinasa (CK), puede conducir a hemodialisis y muerte en los pacientes del servicio de urgencias (SU), pero no se han descritos las caracteristicas del paciente, las enfermedades asociadas y los resultados a los 30 dias de los pacientes con CK mayor de 1.000 U/L. Metodologia Se identificaron retrospectivamente todos los pacientes de forma consecutiva del SU con CK serica mayor a 1.000 U/L de dos hospitales urbanos, entre el 1 de enero de 2006 y el 31 diciembre de 2008. Se determinaron mediante la revision de las historias clinicas las caracteristicas del paciente, el tratamiento del SU y los diagnosticos al alta del SU. Se vincularon las bases de datos a nivel provincial para identificar los pacientes que fallecieron o se trataron con hemodialisis en los primeros 30 dias. El resultado principal fue la ocurrencia combinada de muerte o necesidad de hemodialisis en los primeros 30 dias. Los resultados secundarios incluyeron la incidencia de insuficiencia renal aguda y la proporcion de pacientes con una tasa estimada de filtrado glomerular inicial (TFG) > 60 mL/min/1,73m2 que fallecieron o requirieron hemodialisis. Resultados Se identificaron 400 pacientes, la mediana de edad fue de 50 anos (RIC 35–69 anos) y un 77% fueron varones, con un 35% de los pacientes dados de alta desde el SU. Los diagnosticos mas comunes al alta del SU se relacionaron con el consumo recreativo de drogas, las infecciones y los motivos de consulta musculo-esqueleticos o traumaticos. En los primeros 30 dias, 32 (8,0%, IC 95% = 5,3% a 11%) experimentaron un resultado principal, 18 (4,5%, IC 95% = 2,55 a 6,5%) requirieron hemodialisis y 21 fallecieron (5,3%, IC 95% = 3,1% a 7,4%). La insuficiencia renal aguda ocurrio en 151 pacientes (38%, IC 95%: 33% a 43%). De los 257 pacientes (64%) con una TFG estimada inicial > 60 mL/min/1,73 m2, ninguno requirio hemodialisis. Conclusiones En los pacientes del SU con una CK inicial > 1.000 U/L, la incidencia de muerte o hemodialisis fue de un 8% en los primeros 30 dias. Los pacientes con una TFG estimada inicial > 60 mL/min/1,73m2 parecen tener un bajo riesgo.

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.

The effectiveness of traditional adherence measurements used in adolescent populations is difficult to assess. Antiretroviral (ARV) adherence research among adolescents living with HIV in resource-constrained countries is particularly challenging and little evidence is available. The primary objective of this study was to determine the feasibility of a large-scale, long-term study using electronic adherence monitoring in Uganda. The secondary objective was to compare accuracy of pill count (PC) and self-report (SR) adherence with electronic medication vials (eCAPs™). Adolescents receiving ARV therapy at the Joint Clinical Research Centre in Kampala, Uganda, were recruited. ARVs were dispensed in eCAPs™ for 1 year. Person-pill-days (PPDs) [1 day where adherence was measured for one medication in one patient] were calculated and a weighted paired t-test was used to compare the levels of adherence among subjects for three different adherence measurement methods. Fifteen patients were included: 40% were female, mean age was 14 years, mean baseline CD4+ cell count was 244 cells/μL, and average treatment duration was 9 months at study entry. Overall, 4721 PPDs were observed. Some eCAPs™ required replacement during the study resulting in some data loss. Consent rate was high (94%) but was slow due to age limit cut-points. Overall adherence for SR was 99%, PC was 97% and eCAP™ was 88% (p