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Background: Sepsis is a leading cause of paediatric mortality worldwide, disproportionately affecting children in low- and middle-income countries. The impacts of climate change on the burden and outcomes of sepsis in low- and middle-income countries, particularly in paediatric populations, remain poorly understood. We aimed to assess the associations between climate variables (temperature and precipitation) and paediatric sepsis incidence and mortality in Bangladesh, one of the countries most affected by climate change. Methods: We conducted retrospective analyses of patient-level data from the International Centre for Diarrhoeal Disease Research, Bangladesh, and environmental data from the National Oceanic and Atmospheric Administration. Using random forests, we assessed associations between sepsis incidence and sepsis mortality with temperature and precipitation between 2009-22. Results: A nonlinear relationship between temperature and sepsis incidence and mortality was identified. The lowest incidence occurred at an optimum temperature of 26.6°C with a gradual increase below and a sharp rise above this temperature. Higher precipitation levels showed a general trend of increased sepsis incidence. A similar distribution for sepsis mortality was identified with an optimum temperature of 28°C. Conclusions: Findings suggest that environmental temperature and precipitation play a role in paediatric sepsis incidence and sepsis mortality in Bangladesh. As children are particularly vulnerable to climate impacts, it is important to consider climate change in health care planning and resource allocation, especially in resource-limited settings, to allow for surge capacity planning during warmer and wetter seasons. Further prospective research from more globally representative data sets will provide more robust evidence on the nature of the relationships between climate variables and paediatric sepsis worldwide.

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Background: Global emergency medicine (GEM) is situated at the intersection of global health and emergency medicine (EM), which is built upon a history of colonial systems and institutions that continue to reinforce inequities between high-income countries (HICs) and low- and middle-income countries (LMICs) today. These power imbalances yield disparities in GEM practice, research, and education. Approach: The Global Emergency Medicine Academy (GEMA) of the Society for Academic Emergency Medicine formed the Decolonizing GEM Working Group in 2020, which now includes over 100 worldwide members. The mission is to address colonial legacies in GEM and catalyze sustainable changes and recommendations toward decolonization at individual and institutional levels. To develop recommendations to decolonize GEM, the group conducted a nonsystematic review of existing literature on decolonizing global health, followed by in-depth discussions between academics from LMICs and HICs to explore implications and challenges specific to GEM. We then synthesized actionable solutions to provide recommendations on decolonizing GEM. Results: Despite the rapidly expanding body of literature on decolonizing global health, there is little guidance specific to the relatively new field of GEM. By applying decolonizing principles to GEM, we suggest key priorities for improving equity in academic GEM: (1) reframing partnerships to place LMIC academics in positions of expertise and power, (2) redirecting research funding toward LMIC-driven projects and investigators, (3) creating more equitable practices in establishing authorship, and (4) upholding principles of decolonization in the education of EM trainees from LMICs and HICs. Conclusions: Understanding the colonial roots of GEM will allow us to look more critically at current health disparities and identify inequitable institutionalized practices within our profession that continue to uphold these misguided concepts. A decolonized future of GEM depends on our recognition and rectification of colonial-era practices that shape structural determinants of health care delivery and scientific advancement.

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The tenth Ebola Virus Disease (EVD) outbreak (2018-2020, North Kivu, Ituri, South Kivu) in the Democratic Republic of the Congo (DRC) was the second-largest EVD outbreak in history. During this outbreak, Ebola vaccination was an integral part of the EVD response. We evaluated community perceptions toward Ebola vaccination and identified correlates of Ebola vaccine uptake among high-risk community members in North Kivu, DRC. In March 2021, a cross-sectional survey among adults was implemented in three health zones. We employed a sampling approach mimicking ring vaccination, targeting EVD survivors, their household members, and their neighbors. Outbreak experiences and perceptions toward the Ebola vaccine were assessed, and modified Poisson regression was used to identify correlates of Ebola vaccine uptake among those offered vaccination. Among the 631 individuals surveyed, most (90.2%) reported a high perceived risk of EVD and 71.6% believed that the vaccine could reduce EVD severity; however, 63.7% believed the vaccine had serious side effects. Among the 474 individuals who had been offered vaccination, 397 (83.8%) received the vaccine, 180 (45.3%) of those vaccinated received the vaccine after two or more offers. Correlates positively associated with vaccine uptake included having heard positive information about the vaccine (RR 1.30, 95% CI 1.06-1.60), the belief that the vaccine could prevent EVD (RR 1.23, 95% CI 1.09-1.39), and reporting that religion influenced all decisions (RR 1.13, 95% CI 1.02-1.25). Ebola vaccine uptake was high in this population, although mixed attitudes and vaccine delays were common. Communicating positive vaccine information, emphasizing the efficacy of the Ebola vaccine, and engaging religious leaders to promote vaccination may aid in increasing Ebola vaccine uptake during future outbreaks.

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BACKGROUND: Despite the importance of accurate and rapid assessment of hydration status in patients with acute diarrhoea, no validated tools exist to help clinicians assess dehydration severity in older children and adults. The aim of this study is to validate a clinical decision support tool (CDST) and a simplified score for dehydration severity in older children and adults with acute diarrhoea (both developed during the NIRUDAK study) and compare their accuracy and reliability with current WHO guidelines. METHODS: A random sample of patients aged 5 years or older presenting with diarrhoea to the icddr,b Dhaka Hospital in Bangladesh between Jan 30 and Dec 13, 2022 were included in this prospective cohort study. Patients with fewer than three loose stools per day, more than 7 days of symptoms, previous enrolment in the study, or a diagnosis other than acute gastroenteritis were excluded. Patients were weighed on arrival and assessed separately by two nurses using both our novel clinical tools and WHO guidelines. Patients were weighed every 4 h to determine their percent weight change with rehydration, our criterion standard for dehydration. Accuracy for the diagnosis of dehydration category (none, some, or severe) was assessed using the ordinal c-index (ORC). Reliability was assessed by comparing the prediction of severe dehydration from each nurse's independent assessment using the intraclass correlation coefficient (ICC). FINDINGS: 1580 patients were included in our primary analysis, of whom 921 (58·3%) were female and 659 (41·7%) male. The ORC was 0·74 (95% CI 0·71-0·77) for the CDST, 0·75 (0·71-0·78) for the simplified score, and 0·64 (0·61-0·67) for the WHO guidelines. The ICC was 0·98 (95% CI 0·97-0·98) for the CDST, 0·94 (0·93-0·95) for the simplified score, and 0·56 (0·52-0·60) for the WHO guidelines. INTERPRETATION: Use of our CDST or simplified score by clinicians could reduce undertreatment and overtreatment of older children and adults with acute diarrhoea, potentially reducing morbidity and mortality for this common disease. FUNDING: US National Institutes of Health. TRANSLATION: For the Bangla translation of the abstract see Supplementary Materials section.

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Introduction: During the 2018-2020 Ebola virus disease (EVD) outbreak in the eastern part of the Democratic Republic of the Congo (DRC), prevention and control measures, such as Ebola vaccination were challenging by community mistrust. We aimed to understand perceptions regarding Ebola vaccination and identify determinants of Ebola vaccine uptake among HCWs. Methods: In March 2021, we conducted a cross-sectional survey among 438 HCWs from 100 randomly selected health facilities in three health zones (Butembo, Beni, Mabalako) affected by the 10th EVD outbreak in North Kivu, DRC. HCWs were eligible if they were ≥ 18 years and were working in a health facility during the outbreak. We used survey logistic regression to assess correlates of first-offer uptake (i.e., having received the vaccine the first time it was offered vs. after subsequent offers). Results: Of the 438 HCWs enrolled in the study, 420 (95.8%) reported that they were eligible and offered an Ebola vaccine. Among those offered vaccination, self-reported uptake of the Ebola vaccine was 99.0% (95% confidence interval (CI) [98.5-99.4]), but first-offer uptake was 70.2% (95% CI [67.1, 73.5]). Nearly all HCWs (94.3%; 95% CI [92.7-95.5]) perceived themselves to be at risk of contracting EVD. The most common concern was that the vaccine would cause side effects (65.7%; 95% CI [61.4-69.7]). In the multivariable analysis, mistrust of the vaccine source or how the vaccine was produced decreased the odds of first-time uptake. Discussion: Overall uptake of the Ebola vaccine was high among HCWs, but uptake at the first offer was substantially lower, which was associated with mistrust of the vaccine source. Future Ebola vaccination efforts should plan to make repeated vaccination offers to HCWs and address their underlying mistrust in the vaccines, which can, in turn, improve community uptake.

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Background: Antibiotics are commonly overused for diarrheal illness in many low- and middle-income countries, partly due to a lack of diagnostics to identify viral cases, in which antibiotics are not beneficial. This study aimed to develop clinical prediction models to predict risk of viral-only diarrhea across all ages, using routinely collected demographic and clinical variables. Methods: We used a derivation dataset from 10 hospitals across Bangladesh and a separate validation dataset from the icddr,b Dhaka Hospital. The primary outcome was viral-only etiology determined by stool quantitative polymerase chain reaction. Multivariable logistic regression models were fit and externally validated; discrimination was quantified using area under the receiver operating characteristic curve (AUC) and calibration assessed using calibration plots. Results: Viral-only diarrhea was common in all age groups (<1 year, 41.4%; 18-55 years, 17.7%). A forward stepwise model had AUC of 0.82 (95% confidence interval [CI], .80-.84) while a simplified model with age, abdominal pain, and bloody stool had AUC of 0.81 (95% CI, .78-.82). In external validation, the models performed adequately although less robustly (AUC, 0.72 [95% CI, .70-.74]). Conclusions: Prediction models consisting of 3 routinely collected variables can accurately predict viral-only diarrhea in patients of all ages in Bangladesh and may help support efforts to reduce inappropriate antibiotic use.

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INTRODUCTION: Acute diarrhea remains a leading cause of morbidity and mortality with over 6.3 billion cases and 1.3 million deaths annually. Despite the existence of standardized guidelines for diarrhea management, wide variability in clinical practice exists, particularly in resource-limited settings. The goal of this study was to qualitatively explore how diarrhea management in Bangladesh varies according to resource availability, clinical setting, and provider roles. METHODOLOGY: This was a secondary analysis of a cross-sectional qualitative study conducted in three diverse hospital settings (district hospital, subdistrict hospital, and specialty diarrhea research hospital) in Bangladesh. A total of eight focus group discussions with nurses and physicians were conducted. Applied thematic analysis was used to identify themes regarding variations in diarrhea management. RESULTS: Of the 27 focus group participants, 14 were nurses and 13 doctors; 15 worked in a private diarrhea specialty hospital and 12 worked in government district or subdistrict hospitals. Several key themes emerged from the qualitative data analysis: 1) priorities in the clinical assessment of diarrhea 2) use of guidelines versus clinical judgment; 3) variability in clinician roles and between clinical settings influences care delivery; 4) impact of resource availability on diarrhea management; and 5) perceptions of community health workers' role in diarrhea management. CONCLUSIONS: Findings from this study may aid in informing interventions to improve and standardize diarrhea management in resource-constrained settings. Resource availability, practices regarding diarrhea assessment and treatment, provider experience, and variability in provider roles are essential considerations when developing clinical tools in low- and middle- income countries.

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Background: Severe acute respiratory infections (SARIs) are the leading cause of paediatric death globally, particularly in low- and middle-income countries (LMICs). Given the potential rapid clinical decompensation and high mortality rate from SARIs, interventions that facilitate the early care are critical to improving patient outcomes. Through this systematic review, we aimed to evaluate the impact of emergency care interventions on improving clinical outcomes of paediatric patients with SARIs in LMICs. Methods: We searched PubMed, Global Health, and Global Index Medicus for peer-reviewed clinical trials or studies with comparator groups published before November 2020. We included all studies which evaluated acute and emergency care interventions on clinical outcomes for children (29 days to 19 years) with SARIs conducted in LMICs. Due to observed heterogeneity of interventions and outcomes, we performed narrative synthesis. We assessed bias using the Risk of Bias 2 and Risk of Bias in Non-Randomized Studies of Interventions tools. Results: We screened 20 583, 99 of which met the inclusion criteria. Conditions studied included pneumonia or acute lower respiratory infection (61.6%) and bronchiolitis (29.3%). Studies evaluated medications (80.8%), respiratory support (14.1%), and supportive care (5%). We found the strongest evidence of benefit for decreasing risk of death for respiratory support interventions. Results were inconclusive on the utility of continuous positive airway pressure (CPAP). We found mixed results for interventions for bronchiolitis, but a possible benefit for hypertonic nebulised saline to decrease hospital length of stay. Early use of adjuvant treatments such as Vitamin A, D, and zinc for pneumonia and bronchiolitis did not appear to have convincing evidence of benefit on clinical outcomes. Conclusions: Despite the high global burden of SARI in paediatric populations, few emergency care (EC) interventions have high quality evidence for benefit on clinical outcomes in LMICs. Respiratory support interventions have the strongest evidence for benefit. Further research on the use of CPAP in diverse settings is needed, as is a stronger evidence base for EC interventions for children with SARI, including metrics on the timing of interventions. Registration: PROSPERO (CRD42020216117).

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Populations affected by humanitarian crises and emerging infectious disease outbreaks may have unique concerns and experiences that influence their perceptions toward vaccines. In March 2021, we conducted a survey to examine the perceptions toward COVID-19 vaccines and identify the factors associated with vaccine intention among 631 community members (CMs) and 438 healthcare workers (HCWs) affected by the 2018-2020 Ebola Virus Disease outbreak in North Kivu, Democratic Republic of the Congo. A multivariable logistic regression was used to identify correlates of vaccine intention. Most HCWs (81.7%) and 53.6% of CMs felt at risk of contracting COVID-19; however, vaccine intention was low (27.6% CMs; 39.7% HCWs). In both groups, the perceived risk of contracting COVID-19, general vaccine confidence, and male sex were associated with the intention to get vaccinated, with security concerns preventing vaccine access being negatively associated. Among CMs, getting the Ebola vaccine was associated with the intention to get vaccinated (RR 1.43, 95% CI 1.05-1.94). Among HCWs, concerns about new vaccines' safety and side effects (OR 0.72, 95% CI 0.57-0.91), religion's influence on health decisions (OR 0.45, 95% CI 0.34-0.61), security concerns (OR 0.52, 95% CI 0.37-0.74), and governmental distrust (OR 0.50, 95% CI 0.35-0.70) were negatively associated with vaccine perceptions. Enhanced community engagement and communication that address this population's concerns could help improve vaccine perceptions and vaccination decisions. These findings could facilitate the success of vaccine campaigns in North Kivu and similar settings.

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Objective: Framework Matrix Analysis (FMA) and Applied Thematic Analysis (ATA) are qualitative methods that have not been as widely used/cited compared to content analysis or grounded theory. This paper compares methods of FMA with ATA for mobile health (mHealth) research. The same qualitative data were analyzed separately, using each methodology. The methods, utility, and results of each are compared, and recommendations made for their effective use. Methods: Formative qualitative data were collected in eight focus group discussions with physicians and nurses from three hospitals in Bangladesh. Focus groups were conducted via video conference in the local language, Bangla, and audio recorded. Audio recordings were used to complete a FMA of participants' opinions about key features of a novel mHealth application (app) designed to support clinical management in patients with acute diarrhea. The resulting framework matrix was shared with the app design team and used to guide iterative development of the product for a validation study of the app. Subsequently, focus group audio recordings were transcribed in Bangla then translated into English for ATA; transcripts and codes were entered into NVivo qualitative analysis software. Code summaries and thematic memos explored the clinical utility of the mHealth app including clinicians' attitudes about using this decision support tool. Results: Each of the two methods contributes differently to the research goal and have different implications for an mHealth research timeline. Recommendations for the effective use of each method in app development include: using FMA for data reduction where specific outcomes are needed to make programming and design decisions and using ATA to capture the more nuanced issues that guide use, product implementation, training, and workflow. Conclusions: By describing how both analytical methods were used in this context, this paper provides guidance and an illustration for use of these two methods, specifically in mHealth design.

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[This corrects the article DOI: 10.1371/journal.pntd.0009266.].

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Background: Severe acute respiratory infections (SARIs) remain a leading cause of death globally, particularly in low- and middle-income countries (LMICs). Early intervention is critical, considering the potential for rapid decompensation in patients with SARIs. We aimed to evaluate the impact of acute and emergency care interventions on improving clinical outcomes in patients >10 years old with SARIs in LMICs. Methods: A systematic literature search was performed in PubMed, Global Health, and Global Index Medicus databases to identify peer-reviewed studies containing SARI, LMICs, and emergency care interventions. Studies published prior to November 2020 focusing on patients >10 years old were included. A narrative synthesis was performed due to the heterogeneity of identified articles. Risk of bias was assessed using the Risk of Bias 2 and Risk of Bias In Non-Randomized Studies of Interventions tools. Results: 20 223 studies were screened and 58 met the inclusion criteria. Thirty-four studies focused on coronavirus-2019 (COVID-19), 15 on pneumonia, seven on influenza, one study on severe acute respiratory syndrome, and one on undifferentiated SARI. Few COVID-19 studies found a benefit of the tested intervention on clinical status, mortality, or hospital length-of-stay. Little to no benefit was found for azithromycin, convalescent plasma, or zinc, and potential harm was found for hydroxychloroquine/chloroquine. There was mixed evidence for immunomodulators, traditional Chinese medicine, and corticosteroids among COVID-19 studies, with notable confounding due to a lack of consistency of control group treatments. Neuraminidase inhibitor antivirals for influenza had the highest quality of evidence for shortening symptom duration and decreasing disease severity. Conclusions: We found few interventions for SARIs in LMICs with have high-quality evidence for improving clinical outcomes. None of the included studies evaluated non-pharmacologic interventions or were conducted in low-income countries. Further studies evaluating the impact of antivirals, immunomodulators, corticosteroids, and non-pharmacologic interventions for SARIs in LMICs are urgently needed. Registration: PROSPERO registration number: CRD42020216117.

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Vaccine hesitancy among displaced populations is associated with inequitable access to services and mistrust of authorities, among other factors. This study evaluated variations in attitudes toward COVID-19 vaccines and factors associated with vaccine acceptance among refugees and Lebanese nationals accessing 60 International Medical Corps-supported health facilities through two cross-sectional surveys pre- (n = 3927; Survey 1) and post- (n = 4174; Survey 2) vaccine rollout. Logistic regression was used to assess predictors of vaccine acceptance using the health beliefs model. Refugees comprised 52.9% (Survey 1) and 54.2% (Survey 2) of respondents. Vaccine acceptance was low among both groups in Survey 1 (25.9% refugees vs. 23.1% Lebanese nationals), but higher in Survey 2 in Lebanese (57.6%) versus refugees (32.9%). Participants reported greater perceived benefits of vaccination, higher perceived COVID-19 susceptibility, and lower perceived vaccination barriers in Survey 2 versus Survey 1. Post-vaccine rollout, refugees had lower odds of vaccine acceptance compared to Lebanese (OR 0.50, 95%CI 0.41-0.60), while older age (OR 1.37, 95%CI 1.06-1.78, ≥51 years vs. 18-30 years) was associated with greater vaccine acceptance. Health beliefs model variables were associated with vaccine acceptance in both surveys. Tailored strategies to respond dynamically to changes in vaccine attitudes among vulnerable groups in Lebanon are essential for equitable vaccine uptake.

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INTRODUCTION: High-income country (HIC) authors are disproportionately represented in authorship bylines compared with those affiliated with low and middle-income countries (LMICs) in global health research. An assessment of authorship representation in the global emergency medicine (GEM) literature is lacking but may inform equitable academic collaborations in this relatively new field. METHODS: We conducted a bibliometric analysis of original research articles reporting studies conducted in LMICs from the annual GEM Literature Review from 2016 to 2020. Data extracted included study topic, journal, study country(s) and region, country income classification, author order, country(s) of authors' affiliations and funding sources. We compared the proportion of authors affiliated with each income bracket using Χ2 analysis. We conducted logistic regression to identify factors associated with first or last authorship affiliated with the study country. RESULTS: There were 14 113 authors in 1751 articles. Nearly half (45.5%) of the articles reported work conducted in lower middle-income countries (MICs), 23.6% in upper MICs, 22.5% in low-income countries (LICs). Authors affiliated with HICs were most represented (40.7%); 26.4% were affiliated with lower MICs, 17.4% with upper MICs, 10.3% with LICs and 5.1% with mixed affiliations. Among single-country studies, those without any local authors (8.7%) were most common among those conducted in LICs (14.4%). Only 31.0% of first authors and 21.3% of last authors were affiliated with LIC study countries. Studies in upper MICs (adjusted OR (aOR) 3.6, 95% CI 2.46 to 5.26) and those funded by the study country (aOR 2.94, 95% CI 2.05 to 4.20) had greater odds of having a local first author. CONCLUSIONS: There were significant disparities in authorship representation. Authors affiliated with HICs more commonly occupied the most prominent authorship positions. Recognising and addressing power imbalances in international, collaborative emergency medicine (EM) research is warranted. Innovative methods are needed to increase funding opportunities and other support for EM researchers in LMICs, particularly in LICs.

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Introduction: In high-income settings, vasopressor administration to treat haemodynamic instability through a central venous catheter (CVC) is the preferred standard. However, due to lack of availability and potential for complications, CVCs are not widely used in low- and middle-income countries. This prospective cohort study evaluated the use of peripheral vasopressors and associated incidence of extravasation events in patients with haemodynamic instability at the Centre Hospitalier Universitaire Kigali, Rwanda. Methods: Patients ≥18 years of age receiving peripheral vasopressors in the emergency centre (EC) or intensive care unit (ICU) for >1 hour were eligible for inclusion. The primary outcome was extravasation events. Patients were followed hourly until extravasation, medication discontinuation, death, or CVC placement. Extravasation incidence with 95% confidence intervals (CI) were calculated using Poisson exact tests. Results: 64 patients were analysed. The median age was 49 (Interquartile Range [IQR]:33-65) and 55% were female. Distributive shock was the most frequent aetiology (47%). Intravenous (IV) location was most commonly antecubital fossa/upper arm (31%) and forearm/hand (43%). IV gauges ≤18 were used in 58% of locations. Most patients were treated with adrenaline (66%) and noradrenaline (41%), and 11% received multiple vasopressors. The median treatment duration was 19 hours (IQR:8.5-37). Treatment discontinuation was predominantly due to mortality (41%) or resolution of instability (36%). There were two extravasation events (2.9%), both limited to soft tissue swelling. Extravasation incidence was 0.8 events per 1000 patient-hours (95% CI:0.2-2.2). Conclusion: Extravasation incidence with peripheral vasopressors was low, even with long use durations, suggesting peripheral infusions may be an acceptable approach when barriers exist to CVC placement.

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BACKGROUND: The availability of mobile clinical decision support (CDS) tools has grown substantially with the increased prevalence of smartphone devices and apps. Although health care providers express interest in integrating mobile health (mHealth) technologies into their clinical settings, concerns have been raised, including perceived disagreements between information provided by mobile CDS tools and standard guidelines. Despite their potential to transform health care delivery, there remains limited literature on the provider's perspective on the clinical utility of mobile CDS tools for improving patient outcomes, especially in low- and middle-income countries. OBJECTIVE: This study aims to describe providers' perceptions about the utility of a mobile CDS tool accessed via a smartphone app for diarrhea management in Bangladesh. In addition, feedback was collected on the preliminary components of the mobile CDS tool to address clinicians' concerns and incorporate their preferences. METHODS: From November to December 2020, qualitative data were gathered through 8 web-based focus group discussions with physicians and nurses from 3 Bangladeshi hospitals. Each discussion was conducted in the local language-Bangla-and audio recorded for transcription and translation by the local research team. Transcripts and codes were entered into NVivo (version 12; QSR International), and applied thematic analysis was used to identify themes that explore the clinical utility of an mHealth app for assessing dehydration severity in patients with acute diarrhea. Summaries of concepts and themes were generated from reviews of the aggregated coded data; thematic memos were written and used for the final analysis. RESULTS: Of the 27 focus group participants, 14 (52%) were nurses and 13 (48%) were physicians; 15 (56%) worked at a diarrhea specialty hospital and 12 (44%) worked in government district or subdistrict hospitals. Participants' experience in their current position ranged from 2 to 14 years, with an average of 10.3 (SD 9.0) years. Key themes from the qualitative data analysis included current experience with CDS, overall perception of the app's utility and its potential role in clinical care, barriers to and facilitators of app use, considerations of overtreatment and undertreatment, and guidelines for the app's clinical recommendations. Participants felt that the tool would initially take time to use, but once learned, it could be useful during epidemic cholera. Some felt that clinical experience remains an important part of treatment that can be supplemented, but not replaced, by a CDS tool. In addition, diagnostic information, including mid-upper arm circumference and blood pressure, might not be available to directly inform programming decisions. CONCLUSIONS: Participants were positive about the mHealth app and its potential to inform diarrhea management. They provided detailed feedback, which developers used to revise the mobile CDS tool. These formative qualitative data provided timely and relevant feedback to improve the utility of a CDS tool for diarrhea treatment in Bangladesh.

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Background: Diarrheal illness is a leading cause of antibiotic use for children in low- and middle-income countries. Determination of diarrhea etiology at the point-of-care without reliance on laboratory testing has the potential to reduce inappropriate antibiotic use. Methods: This prospective observational study aimed to develop and externally validate the accuracy of a mobile software application ('App') for the prediction of viral-only etiology of acute diarrhea in children 0-59 months in Bangladesh and Mali. The App used a previously derived and internally validated model consisting of patient-specific ('present patient') clinical variables (age, blood in stool, vomiting, breastfeeding status, and mid-upper arm circumference) as well as location-specific viral diarrhea seasonality curves. The performance of additional models using the 'present patient' data combined with other external data sources including location-specific climate, data, recent patient data, and historical population-based prevalence were also evaluated in secondary analysis. Diarrhea etiology was determined with TaqMan Array Card using episode-specific attributable fraction (AFe) >0.5. Results: Of 302 children with acute diarrhea enrolled, 199 had etiologies above the AFe threshold. Viral-only pathogens were detected in 22% of patients in Mali and 63% in Bangladesh. Rotavirus was the most common pathogen detected (16% Mali; 60% Bangladesh). The present patient+ viral seasonality model had an AUC of 0.754 (0.665-0.843) for the sites combined, with calibration-in-the-large α = -0.393 (-0.455--0.331) and calibration slope ß = 1.287 (1.207-1.367). By site, the present patient+ recent patient model performed best in Mali with an AUC of 0.783 (0.705-0.86); the present patient+ viral seasonality model performed best in Bangladesh with AUC 0.710 (0.595-0.825). Conclusions: The App accurately identified children with high likelihood of viral-only diarrhea etiology. Further studies to evaluate the App's potential use in diagnostic and antimicrobial stewardship are underway. Funding: Funding for this study was provided through grants from the Bill and Melinda GatesFoundation (OPP1198876) and the National Institute of Allergy and Infectious Diseases (R01AI135114). Several investigators were also partially supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116163). This investigation was also supported by the University of Utah Population Health Research (PHR) Foundation, with funding in part from the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002538. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the study design, data collection, data analysis, interpretation of data, or in the writing or decision to submit the manuscript for publication.

Diarrhea is one of the most common illnesses among children worldwide. In low- and middle-income countries with limited health care resources, it can be deadly. Diarrhea can be caused by infections with viruses or bacteria. Antibiotics can treat bacterial infections, but they are not effective against viral infections. It can often be difficult to determine the cause of diarrhea. As a result, many clinicians just prescribe antibiotics. However, since diarrhea in young children is often due to viral infections, prescribing unnecessary antibiotics can cause children to have side effects without any benefit. Excessive use of antibiotics also contributes to the development of bacteria that are resistant to antibiotics, making infections harder to treat. Scientists are working to develop mobile health tools or 'apps' that may help clinicians identify the cause of diarrhea. Using computer algorithms to analyze information about the patient and seasonal infection patterns, the apps predict whether a bacterial or viral infection is the likely culprit. These tools may be particularly useful in low- or middle-income country settings, where clinicians have limited access to testing for bacteria or viruses. Garbern, Nelson et al. previously built an app to help distinguish cases of viral diarrhea in children in Mali and Bangladesh. Now, the researchers have put their app to the test in the real-world in a new group of patients to verify it works. In the experiments, nurses in Mali and Bangladesh used the app to predict whether a child with diarrhea had a viral or non-viral infection. The children's stool was then tested for viral or bacterial DNA to confirm whether the prediction was correct. The experiments showed the app accurately identified viral cases of diarrhea. The experiments also showed that customizing the app to local conditions may further improve its accuracy. For example, a version of the app that factored in seasonal virus transmission performed the best in Bangladesh, while a version that factored in data from recent patients in the past few weeks performed the best in Mali. Garbern and Nelson et al. are now testing whether their app could help reduce unnecessary use of antibiotics in children with diarrhea. If it does, it may help minimize antibiotic resistance and ensure more children get appropriate diarrhea care.

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BACKGROUND: Empiric antimalarial treatment is a component of protocol-based management of Ebola virus disease (EVD), yet this approach has limited clinical evidence for patient-centered benefits. METHODS: This retrospective cohort study evaluated the association between antimalarial treatment and mortality among patients with confirmed EVD. The data was collected from five International Medical Corps operated Ebola Treatment Units (ETUs) in Sierra Leone and Liberia from 2014 through 2015. The standardized protocol used for patient care included empiric oral treatment with combination artemether and lumefantrine, twice daily for three days; however, only a subset of patients received treatment due to resource variability. The outcome of interest was mortality, comparing patients treated with oral antimalarials within 48-h of admission to those not treated. Analysis was conducted with logistic regression to generate adjusted odds ratios (aORs). Multivariable analyses controlled for ETU country, malaria rapid diagnostic test result, age, EVD cycle threshold value, symptoms of bleeding, diarrhea, dysphagia and dyspnea, and additional standard clinical treatments. RESULTS: Among the 424 cases analyzed, 376 (88.7%) received early oral antimalarials. Across all cases, mortality occurred in 57.5% (244). In comparing unadjusted mortality prevalence, early antimalarial treated cases yielded 55.1% mortality versus 77.1% mortality for those untreated (p = 0.005). Multivariable analysis demonstrated evidence of reduced aOR for mortality with early oral antimalarial treatment versus non-treatment (aOR = 0.34, 95% Confidence Interval: 0.12, 0.92, p = 0.039). CONCLUSION: Early oral antimalarial treatment in an EVD outbreak was associated with reduced mortality. Further study is warranted to investigate this association between early oral antimalarial treatment and mortality in EVD patients.

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In 2016, diarrheal disease was the eighth leading cause of mortality globally accounting for over 1.6 million deaths with the majority of deaths in adults and children over 5 years. This study aims to investigate the clinical, sociodemographic, and environmental risk factors associated with common bacterial acute diarrhea among adults and children over 5. Data were collected from March 2019 to March 2020 in patients over 5 years presenting with acute gastroenteritis at icddr,b. Stool samples were collected from each patient for culture and polymerase chain reaction (PCR) testing. Bivariate associations between independent variables and stool-testing indicating bacterial etiology were calculated. This analysis included 2,133 diarrheal patients of whom a bacterial enteropathogen was identified in 1,537 (72%). Detection of bacteria was associated with: younger age (OR 0.92; 95% CI: 0.88-0.96), lower mean arterial pressure (OR 0.84; 95% CI: 0.79-0.89), heart rate (OR 1.06; 95% CI: 1.01-1.10), percentage dehydration (OR 1.33; 95% CI: 1.13-1.55), respiration rate (OR 1.23; 95% CI: 1.04-1.46), lower mid-upper arm circumference (OR 0.97; 95% CI: 0.94-0.99), confused/lethargic mental status (OR 1.85; 95% CI: 1.11-3.25), rice watery stool (OR 1.92; 95% CI: 1.54-2.41), and vomiting more than three times in the past 24 hours (OR 1.30; 95% CI: 1.06-1.58). Higher monthly income (OR 0.92; 95% CI: 0.86-0.98), > 8 years of education (OR 0.79; 95% CI: 0.63-1.00), and having more than five people living at home (OR 0.80; 95% CI: 0.66-0.98) were associated with lower odds of bacterial diarrhea. These findings may help guide the development of predictive tools to aid in identifying patients with bacterial diarrhea for timely and appropriate use of antibiotics.

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OBJECTIVE: Accurately assessing dehydration severity is a critical step in reducing mortality from diarrhoea, but is complicated by cholera and undernutrition. This study seeks to assess the accuracy of two clinical diagnostic models for dehydration among patients over five years with cholera and undernutrition and compare their respective performance to the World Health Organization (WHO) algorithm. METHODS: In this secondary analysis of data collected from the NIRUDAK study, accuracy of the full and simplified NIRUDAK models for predicting severe and any dehydration was measured using the area under the Receiver Operator Characteristic curve (AUC) among patients over five with/without cholera and with/without wasting. Bootstrap with 1000 iterations was used to compare the m-index for each NIRUDAK model to that of the WHO algorithm. RESULTS: A total of 2,139 and 2,108 patients were included in the nutrition and cholera subgroups respectively with an overall median age of 35 years (IQR = 42) and 49.6% female. All subgroups had acceptable discrimination in diagnosing severe or any dehydration (AUC > 0.60); though the full NIRUDAK model performed best among patients without cholera, with an AUC of 0.82 (95%CI:0.79, 0.85) and among patients without wasting, with an AUC of 0.79 (95%CI:0.76, 0.81). Compared with the WHO's algorithm, both the full and simplified NIRUDAK models performed significantly better in terms of their m-index (p < 0.001) for all comparisons, except for the simplified NIRUDAK model in the wasting group. CONCLUSIONS: Both the full and simplified NIRUDAK models performed less well in patients over five years with cholera and/or wasting; however, both performed better than the WHO algorithm.

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