Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics.

Early detection of neurofibromatosis type 1 (NF1) associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, potentially averting deadly outcomes. Here, we describe a cell-free DNA (cfDNA) fragmentomic approach which distinguishes non-malignant, pre-malignant and malignant forms of NF1 PNST. Using plasma samples from a novel cohort of 101 NF1 patients and 21 healthy controls, we validated that our previous cfDNA copy number alteration (CNA)-based approach identifies malignant peripheral nerve sheath tumor (MPNST) but cannot distinguish among benign and premalignant states. We therefore investigated the ability of fragment-based cfDNA features to differentiate NF1-associated tumors including binned genome-wide fragment length ratios, end motif analysis, and non-negative matrix factorization deconvolution of fragment lengths. Fragmentomic methods were able to differentiate pre-malignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Overall, this study pioneers the early detection of malignant and premalignant peripheral nerve sheath tumors in NF1 patients using plasma cfDNA fragmentomics. In addition to screening applications, this novel approach distinguishes atypical neurofibromas from benign plexiform neurofibromas and malignant peripheral nerve sheath tumors, enabling more precise clinical diagnosis and management.

Strengthening Mentorship in Global Health for US Medical Students.

US medical students demonstrate strong interest in receiving global health training. In 2012, the Center for Global Health (CGH) at the University of Illinois College of Medicine (UICOM) developed a Global Medicine (GMED) program to match this interest. From its initiation, mentorship has been a key component of the GMED program. More recently, this has been strengthened by applying additional evidence-informed approaches toward mentoring. These include the "mentor up" approach, a "network of mentors," and an individualized development plan (IDP). Applying these changes were associated with increases in the number of student abstract presentations and peer-reviewed journal publications. Mentorship based upon evidence-informed approaches should be a key component of global health education in academic medical centers.

Emergency care of sepsis in sub-Saharan Africa: Mortality and non-physician clinician management of sepsis in rural Uganda from 2010 to 2019.

INTRODUCTION: Little data exists from sub-Saharan Africa describing incidence and outcomes of sepsis in emergency units and uncertainty exists surrounding optimal management of sepsis in low-income settings. There exists limited data regarding quality care metrics for non-physician clinicians trained in emergency care. The objective of this study was to describe changes in septic patients over time and evaluate associations between sepsis care and mortality. METHODS: Secondary analysis of a prospective cohort of all consecutive patients seen from 2010-2019 in a rural Ugandan emergency unit staffed by non-physician clinicians was performed using an electronic database based on paper charts. Sepsis was defined as suspected infection with a quick Sequential Organ Failure Assessment score (qSOFA)≥1. Multi-variable logistic regression was used to analyze three-day mortality. RESULTS: Overall, 48,653 patient visits from 2010-2019 yielded 17,490 encounters for patients age≥18 who had suspected infection, including 10,437 with sepsis. The annual proportion of patients with sepsis decreased from 45.0%% to 21.3% and the proportion with malarial sepsis decreased from 17.7% to 2.1% during the study period. Rates of septic patients receiving quality care ("both fluids and anti-infectives") increased over time (21.2% in 2012 to 32.0% in 2019, p<0.001), but mortality did not significantly improve (4.5% in 2012 to 6.4% in 2019, p = 0.50). The increasing quality of non-physician clinician care was not associated with reduced mortality, and treatment with "both fluids and antibiotics" was associated with increased mortality (RR = 1.55, 95%CI 1.10-2.00). CONCLUSION: The largest study of sepsis management and outcomes ever published in both Uganda and sub-Saharan Africa showed sepsis and malarial sepsis decreasing from 2010 to 2019. The increasing quality of non-physician clinician care did not significantly reduce mortality and treatment with "both fluids and antibiotics" increased mortality. With causal associations between antibiotics and mortality deemed implausible, associations between sepsis mortality and interventions likely represent confounding by indication. Defining optimal sepsis care regionally will likely require randomized controlled trials.

Global Health Education Amidst COVID-19: Disruptions and Opportunities.

This viewpoint examines the impact of COVID-19 travel bans and remote education on the global health education of students from high-income countries (HIC) and low- and middle-income countries (LMIC) and explores potential opportunities for strengthening global health education based upon more dispersed and equitable practices. Global health is unique in the opportunities it can offer to students during the pandemic if programs can manage and learn from the pandemic's many challenges. Global health educators can: shift to sustainable remote engagement and mobilize resources globally to facilitate this; collaborate with partners to support the efforts to deal with the current pandemic and to prepare for its next phases; partner in new ways with health care professional students and faculty from other countries; collaborate in research with partners in studies of pandemic related health disparities in any country; and document and examine the impact of the pandemic on health care workers and students in different global contexts. These strategies can help work around pandemic travel restrictions, overcome the limitations of existing inequitable models of engagement, and better position global health education and face future challenges while providing the needed support to LMIC partners to participate more equally.

Building a virtual community of practice for medical students: The Global Emergency Medicine Student Leadership Program.

Virtual communities of practice (VCoPs) facilitate distance learning and mentorship by engaging members around shared knowledge and experiences related to a central interest. The American College of Emergency Physicians and Emergency Medicine Residents' Association's Global Emergency Medicine Student Leadership Program (GEM-SLP) provides a valuable model for building a VCoP for GEM and other niche areas of interest. This VCoP facilitates opportunities for experts and mentees affiliated with these national organizations to convene regularly despite barriers attributed to physical distance. The GEM-SLP VCoP is built around multiple forms of mentorship, monthly mentee-driven didactics, academic projects, and continued engagement of program graduates in VCoP leadership. GEM-SLP fosters relationships through (1) themed mentoring calls (career paths, work/life balance, etc); (2) functional mentorship through didactics and academic projects; and (3) near-peer mentoring, provided by mentors near the mentees' stage of education and experience. Monthly mentee-driven didactics focus on introducing essential GEM principles while (1) critically analyzing literature based on a journal article; (2) building a core knowledge base from a foundational textbook; (3) applying knowledge and research to a project proposal; and (4) gaining exposure to training and career opportunities via mentor career presentations. Group academic projects provide a true GEM apprenticeship as mentees and mentors work collaboratively. GEM-SLP mentees found the VCoP beneficial in building fundamental GEM skills and knowledge and forming relationships with mentors and like-minded peers. GEM-SLP provides a framework for developing mentorship programs and VCoPs in emergency medicine, especially when niche interests or geographic distance necessitate a virtual format.

A global health capstone: an innovative educational approach in a competency-based curriculum for medical students.

BACKGROUND: Global health educational programs for medical and public health professionals have grown substantially in recent years. The University of Illinois Chicago College of Medicine (UICOM) began a global medicine (GMED) program for selected students in 2012 and has since graduated four classes. As part of the four-year curriculum, students complete a longitudinal global health capstone project. This paper describes the global health capstone project as an innovative educational tool within a competency-based curriculum. METHODS: The authors define and describe the longitudinal global health capstone including specific requirements, student deliverables, and examples of how the global health capstone may be used as part of a larger curriculum to teach the competency domains identified by the Consortium of Universities for Global Health. The authors also reviewed the final capstone projects for 35 graduates to describe characteristics of capstone projects completed. RESULTS: The global health capstone was developed as one educational tool within a broader global health curriculum for medical students. Of the 35 capstones, 26 projects involved original research (74%), and 25 involved international travel (71%). Nine projects led to a conference abstract/presentation (26%) while five led to a publication (14%). Twenty-one projects (60%) had subject matter-focused faculty mentorship. CONCLUSIONS: A longitudinal global health capstone is a feasible tool to teach targeted global health competencies and can provide meaningful opportunities for research and career mentorship. Further refinement of the capstone process is needed to strengthen mentorship, and additional assessment methods are needed.

Managing choledocholithiasis in pregnancy: a novel approach.

The management of choledocholithiasis in pregnancy can present a challenge due to radiation risk to the fetus and the possibility of severe maternal pancreatitis. We describe a case in which both these risks were avoided using a trans-cystic stent placed under endoscopic guidance during laparoscopic cholecystectomy.

White mesentery and chylous ascites: an interesting presentation of mesenteric lymphangioma.

We present an interesting and unusual case of a 57-year-old woman presenting with symptoms concerning for a bowel obstruction, and diagnostic imaging concerning for an internal hernia. The patient underwent an emergency laparotomy and was found to have chylous ascites throughout the abdomen, and the extravasation of chyle into the mesentery giving an appearance of a white mesentery. During this case, we will present all of the findings and discuss the unusual underlying pathology.

A pilot study on the management and outcomes of self-poisoning in a rural Ugandan Emergency Centre.

INTRODUCTION: The Global Emergency Care Collaborative and Nyakibale Hospital in Rukungiri opened the first functional emergency centre in rural Uganda. We investigated decontamination, management and outcomes of poisoned patients in the emergency centre. METHODS: An electronic database started recording charts from 24 March 2012. A search for diagnoses concerning self-poisoning was performed from 24 March 2012 to 30 December 2013 and 192 charts were found and de-identified. Data collection included: age, sex, poison and duration, intent, vital signs, physical examination, decontamination, antidote use and follow-up status. RESULTS: From 24 March 2012 to 30 December 2013 poisoning accounted for 96 patient encounters. Of these, 33 were associated with alpha-2 agonists and 16 were associated with organophosphorous or carbamate pesticides. The post-decontamination fatality rate was 5.7%. The fatality rate of those without decontamination was 8.3%. Of those who were given atropine, 38.8% had no known indication. Of the 96 patient encounters, there were seven deaths; six were due to pesticides. DISCUSSION: In resource-limited settings where antidotes and resuscitative capabilities are scarce, decontamination needs to be studied further. Repeat atropine use without indication may lead to depletion of an essential antidote. Future directions include a public health education programme and an algorithm to help guide clinical decisions.

What resources are used in emergency departments in rural sub-Saharan Africa? A retrospective analysis of patient care in a district-level hospital in Uganda.

OBJECTIVES: To determine the most commonly used resources (provider procedural skills, medications, laboratory studies and imaging) needed to care for patients. SETTING: A single emergency department (ED) of a district-level hospital in rural Uganda. PARTICIPANTS: 26 710 patient visits. RESULTS: Procedures were performed for 65.6% of patients, predominantly intravenous cannulation, wound care, bladder catheterisation and orthopaedic procedures. Medications were administered to 87.6% of patients, most often pain medications, antibiotics, intravenous fluids, antimalarials, nutritional supplements and vaccinations. Laboratory testing was used for 85% of patients, predominantly malaria smears, rapid glucose testing, HIV assays, blood counts, urinalyses and blood type. Radiology testing was performed for 17.3% of patients, including X-rays, point-of-care ultrasound and formal ultrasound. CONCLUSION: This study describes the skills and resources needed to care for a large prospective cohort of patients seen in a district hospital ED in rural sub-Saharan Africa. It demonstrates that the vast majority of patients were treated with a small formulary of critical medications and limited access to laboratories and imaging, but providers require a broad set of decision-making and procedural skills.

Mortality in Children Under Five Receiving Nonphysician Clinician Emergency Care in Uganda.

BACKGROUND: A nonphysician clinician (NPC) training program was started in Uganda in 2009. NPC care was initially supervised by a physician and subsequent care was independent. The mortality of children under 5 (U5) was analyzed to evaluate the impact of transitioning NPC care from physician-supervised to independent care. METHODS: A retrospective review was performed of a quality assurance database including 3-day follow-up for all patients presenting to the emergency department (ED). Mortality rates were calculated and χ(2) tests used for significance of proportions. Multiple logistic regression was used to assess independent predictors of mortality. RESULTS: Overall, 68.8% of 4985 U5 patients were admitted and 28.6% were "severely ill." The overall mortality was significantly lower in physician-supervised versus independent NPC care (2.90% vs 5.04%, P = .05). No significant mortality difference was seen between supervised and unsupervised care (2.17% vs 3.01%, P = .43) for the majority of patients that were not severely ill. Severely ill patients analyzed separately showed a significant mortality difference (4.07% vs 10.3%, P = .01). Logistic regression revealed physician supervision significantly reduced mortality for patients overall (odds ratio = 0.52, P = .03), but not for nonseverely ill patients analyzed separately (odds ratio = 0.73, P = .47). CONCLUSIONS: Though physician supervision reduced mortality for the severely ill subset of patients, physicians are not available full-time in most EDs in Sub-Saharan Africa. Training NPCs in emergency care produced noninferior mortality outcomes for unsupervised NPC care compared with physician-supervised NPC care for the majority of U5 patients.

Mortality related to acute illness and injury in rural Uganda: task shifting to improve outcomes.

BACKGROUND: Due to the dual critical shortages of acute care and healthcare workers in resource-limited settings, many people suffer or die from conditions that could be easily treated if existing resources were used in a more timely and effective manner. In order to address this preventable morbidity and mortality, a novel emergency midlevel provider training program was developed in rural Uganda. This is the first study that assesses this unique application of a task-shifting model to acute care by evaluating the outcomes of 10,105 patients. METHODS: Nurses participated in a two-year training program to become midlevel providers called Emergency Care Practitioners at a rural district hospital. This is a retrospective analysis of the Emergency Department's quality assurance database, including three-day follow-up data. Case fatality rates (CFRs) are reported as the percentage of cases with a specific diagnosis that died within three days of their Emergency Department visit. FINDINGS: Overall, three-day mortality was 2.0%. The most common diagnoses of patients who died were malaria (n=60), pneumonia (n=51), malnutrition (n=21), and trauma (n=18). Overall and under-five CFRs were as follows: malaria, 2.0% and 1.9%; pneumonia, 5.5% and 4.1%; and trauma, 1.2% and 1.6%. Malnutrition-related fatality (all cases <18 years old) was 6.5% overall and 6.8% for under-fives. INTERPRETATION: This study describes the outcomes of emergency patients treated by midlevel providers in a resource-limited setting. Our fatality rates are lower than previously published regional rates. These findings suggest this model of task-shifting can be successfully applied to acute care in order to address the shortage of emergency care services in similar settings as part of an integrated approach to health systems strengthening.

World Health Assembly Resolution 60.22. [corrected].

The World Health Assembly 2007 Resolution 60.22 tasked the global health community to address the lack of emergency care in low- and middle-income countries. Little progress has yet been made in integrating emergency care into most low- and middle-income-country health systems. At a rural Ugandan district hospital, however, a collaborative between a nongovernmental organization and local and national stakeholders has implemented an innovative emergency care training program. To our knowledge, this is the first description of using task shifting in general hospital-based emergency care through creation of a new nonphysician clinician cadre, the emergency care practitioner. The program provides an example of how emergency care can be practically implemented in low-resource settings in which physician numbers are limited. The Ministry of Health is directing its integration into the national health care system as a component of a larger ongoing effort to develop a tiered emergency care system (out-of-hospital, clinic- and hospital-based provider and physician trainings) in Uganda. This tiered emergency care system is an example of a horizontal health system advancement that offers a potentially attractive solution to meet the mandate of World Health Assembly 60.22 by providing inexpensive educational interventions that can make emergency care truly accessible to the rural and urban communities of low- and middle-income countries.

Nurse-administered ketamine sedation in an emergency department in rural Uganda.

STUDY OBJECTIVE: We determine whether, after a brief training program in procedural sedation, nurses can safely independently administer ketamine sedation in a resource-limited environment. METHODS: This is an observational case series of consecutive sedations performed in an emergency department in rural Uganda at approximately 5,000 feet above sea level. The data were collected prospectively in a quality assurance database. As part of a larger training program in emergency care at Karoli Lwanga Hospital in rural Uganda, nurses with no sedation experience were trained in procedural sedation with ketamine. All sedations were monitored by a nonphysician research assistant, who recorded ketamine dosing, duration of each procedure, adverse events, and nurse interventions for each adverse event. In accordance with standard definitions in the emergency medicine sedation literature, adverse events were defined a priori and classified as major (death, need for bag-valve-mask ventilation, or unanticipated admission to the hospital) or minor (hypoxia, vomiting, emergence reactions, hypersalivation). The primary statistical analysis was descriptive, with reporting of adverse event rates with 95% confidence intervals (CIs), using the nurse as the unit of analysis. RESULTS: There were a total of 191 administrations by 6 nurses during the study period (December 2009 through March 2010). Overall, there was an 18% adverse event rate (95% CI 7% to 30%), which is similar to the rate reported in resource-rich countries. These events included hypoxia (22 cases; 12%), vomiting (9 cases; 5%), and emergence reaction (7 cases; 4%). All adverse events met our a priori defined criteria for minor events, with a 0% incidence of major events (1-sided 97.5% CI with the nurse as unit of analysis 0% to 46%). The procedural success rate was 99%. Sedation was practitioner rated as "excellent" in 91% of cases (95% CI 86% to 94%) and "good" in 9% (95% CI 6% to 14%). Patients reported they would want ketamine for a future procedure in 98% of cases (95% CI 95% to 100%). CONCLUSION: In resource-limited settings, nurse-administered ketamine sedation appears to be safe and effective. A brief procedural sedation training program, coupled with a comprehensive training program in emergency care, can increase access to appropriate and safe sedation for patients in resource-limited settings.

Alcohol-related hypoglycemia in rural Uganda: socioeconomic and physiologic contrasts.

Hypoglycemia is a rare but important complication seen in patients who present with alcohol intoxication. In a study by Marks and Teale, less than one percent of people with alcohol intoxication who presented to an American emergency department were hypoglycemic [1]. It is even more rare to see an intoxicated patient, who had been eating appropriately prior to or during the intoxication, present in a hypoglycemic coma. However, our analysis of the first 500 patients seen in a newly opened five-bed Emergency Department (ED) at Nyakibale Karoli Lwanga Hospital in rural southwestern Uganda, revealed multiple intoxicated patients who presented in hypoglycemic coma within hours of eating a full meal. Three of these cases are summarized and discussed below.

Chicago medical response to the 2010 earthquake in Haiti: translating academic collaboration into direct humanitarian response.

On January 12, 2010, a major earthquake in Haiti resulted in approximately 212 000 deaths, 300 000 injuries, and more than 1.2 million internally displaced people, making it the most devastating disaster in Haiti's recorded history. Six academic medical centers from the city of Chicago established an interinstitutional collaborative initiative, the Chicago Medical Response, in partnership with nongovernmental organizations (NGOs) in Haiti that provided a sustainable response, sending medical teams to Haiti on a weekly basis for several months. More than 475 medical volunteers were identified, of whom 158 were deployed to Haiti by April 1, 2010. This article presents the shared experiences, observations, and lessons learned by all of the participating institutions. Specifically, it describes the factors that provided the framework for the collaborative initiative, the communication networks that contributed to the ongoing response, the operational aspects of deploying successive medical teams, and the benefits to the institutions as well as to the NGOs and Haitian medical system, along with the challenges facing those institutions individually and collectively. Academic medical institutions can provide a major reservoir of highly qualified volunteer medical personnel that complement the needs of NGOs in disasters for a sustainable medical response. Support of such collaborative initiatives is required to ensure generalizability and sustainability.