Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase–polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P=0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P=0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.)

As portability and durability improve, bedside, clinician-performed ultrasound is seeing increasing use in rural, underdeveloped parts of the world. Physicians, nurses and medical officers have demonstrated the ability to perform and interpret a large variety of ultrasound exams, and a growing body of literature supports the use of point-of-care ultrasound in developing nations. We review, by region, the existing literature in support of ultrasound use in the developing world and training guidelines currently in use, and highlight indications for emergency ultrasound in the developing world. We suggest future directions for bedside ultrasound use and research to improve diagnostic capacity and patient care in the most remote areas of the globe.

Acute gastroenteritis develops in millions of children in the United States every year, and treatment with probiotics is common. However, data to support the use of probiotics in this population are limited.

Annually, there are about 20 million cases of sepsis, defined as life-threatening acute organ dysfunction caused by a dysregulated host response to infection,¹ leading to more than 5 million deaths, with most of the burden in low- and middle-income countries (LMICs).² There is no reference standard that allows easy, accurate diagnosis of sepsis.^1,3 Although the 1991 International Consensus Definition Task Force proposed the systemic inflammatory response syndrome (SIRS) criteria to identify patients with a septic host response,⁴ these criteria do not measure whether the response is injurious, and their utility is limited.^1,3 In 2016, the Sepsis-3 Task Force proposed that, for patients with suspected infection, an increase of 2 points in the Sequential (Sepsis-Related) Organ Failure Assessment (SOFA) score could serve as clinical criteria for sepsis.¹ This approach was justified based on content validity (SOFA reflects the facets of organ dysfunction) and predictive validity (the proposed criteria predict downstream events associated with the condition of interest).⁵ However, the utility of SOFA is limited outside the intensive care unit (ICU) because many SOFA variables are not measured routinely.

Objectives:  The objective of this study was to determine the test characteristics for two different ultrasound (US) measures of severe dehydration in children (aorta to inferior vena cava [IVC] ratio and IVC inspiratory collapse) and one clinical measure of severe dehydration (the World Health Organization [WHO] dehydration scale).Methods:  The authors enrolled a prospective cohort of children presenting with diarrhea and/or vomiting to three rural Rwandan hospitals. Children were assessed clinically using the WHO scale and then underwent US of the IVC by a second clinician. All children were weighed on admission and then fluid‐resuscitated according to standard hospital protocols. A percent weight change between admission and discharge of greater than 10% was considered the criterion standard for severe dehydration. Receiver operating characteristic (ROC) curves were created for each of the three tests of severe dehydration compared to the criterion standard.Results:  Children ranged in age from 1 month to 10 years; 29% of the children had severe dehydration according to the criterion standard. Of the three different measures of dehydration tested, only US assessment of the aorta/IVC ratio had an area under the ROC curve statistically different from the reference line. At its best cut‐point, the aorta/IVC ratio had a sensitivity of 93% and specificity of 59%, compared with 93% and 35% for IVC inspiratory collapse and 73% and 43% for the WHO scale.Conclusions:  Ultrasound of the aorta/IVC ratio can be used to identify severe dehydration in children presenting with acute diarrhea and may be helpful in guiding clinical management.ACADEMIC EMERGENCY MEDICINE 2010; 17:1035–1041 © 2010 by the Society for Academic Emergency Medicine

The 2013-16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive care to patients admitted to Ebola treatment units. Key recommendations include administration of oral and, as necessary, intravenous hydration; systematic monitoring of vital signs and volume status; availability of key biochemical testing; adequate staffing ratios; and availability of analgesics, including opioids, for pain relief.