Development and Validation of Manually Modified and Supervised Machine Learning Clinical Assessment Algorithms for Malaria in Nigerian Children.

It is currently estimated that 67% of malaria deaths occur in children under-five years (WHO, 2020). To improve the identification of children at clinical risk for malaria, the WHO developed community (iCCM) and clinic-based (IMCI) protocols for frontline health workers using paper-based forms or digital mobile health (mHealth) platforms. To investigate improving the accuracy of these point-of-care clinical risk assessment protocols for malaria in febrile children, we embedded a malaria rapid diagnostic test (mRDT) workflow into THINKMD's (IMCI) mHealth clinical risk assessment platform. This allowed us to perform a comparative analysis of THINKMD-generated malaria risk assessments with mRDT truth data to guide modification of THINKMD algorithms, as well as develop new supervised machine learning (ML) malaria risk algorithms. We utilized paired clinical data and malaria risk assessments acquired from over 555 children presenting to five health clinics in Kano, Nigeria to train ML algorithms to identify malaria cases using symptom and location data, as well as confirmatory mRDT results. Supervised ML random forest algorithms were generated using 80% of our field-based data as the ML training set and 20% to test our new ML logic. New ML-based malaria algorithms showed an increased sensitivity and specificity of 60 and 79%, and PPV and NPV of 76 and 65%, respectively over THINKD initial IMCI-based algorithms. These results demonstrate that combining mRDT "truth" data with digital mHealth platform clinical assessments and clinical data can improve identification of children with malaria/non-malaria attributable febrile illnesses.

Development and Initial Validation of a Frontline Health Worker mHealth Assessment Platform (MEDSINC®) for Children 2-60 Months of Age.

Approximately 3 million children younger than 5 years living in low- and middle-income countries (LMICs) die each year from treatable clinical conditions such as pneumonia, dehydration secondary to diarrhea, and malaria. A majority of these deaths could be prevented with early clinical assessments and appropriate therapeutic intervention. In this study, we describe the development and initial validation testing of a mobile health (mHealth) platform, MEDSINC®, designed for frontline health workers (FLWs) to perform clinical risk assessments of children aged 2-60 months. MEDSINC is a web browser-based clinical severity assessment, triage, treatment, and follow-up recommendation platform developed with physician-based Bayesian pattern recognition logic. Initial validation, usability, and acceptability testing were performed on 861 children aged between 2 and 60 months by 49 FLWs in Burkina Faso, Ecuador, and Bangladesh. MEDSINC-based clinical assessments by FLWs were independently and blindly correlated with clinical assessments by 22 local health-care professionals (LHPs). Results demonstrate that clinical assessments by FLWs using MEDSINC had a specificity correlation between 84% and 99% to LHPs, except for two outlier assessments (63% and 75%) at one study site, in which local survey prevalence data indicated that MEDSINC outperformed LHPs. In addition, MEDSINC triage recommendation distributions were highly correlated with those of LHPs, whereas usability and feasibility responses from LHP/FLW were collectively positive for ease of use, learning, and job performance. These results indicate that the MEDSINC platform could significantly increase pediatric health-care capacity in LMICs by improving FLWs' ability to accurately assess health status and triage of children, facilitating early life-saving therapeutic interventions.

A phase 1 study of nifurtimox in patients with relapsed/refractory neuroblastoma.

The primary aim of this phase 1 study was to determine the maximum tolerated dose (MTD) and evaluate the safety of nifurtimox alone and in combination with cyclophosphamide and topotecan in multiple relapsed/refractory neuroblastoma pediatric patients. The secondary aim was to evaluate the pharmacokinetics of nifurtimox and the treatment response. To these ends, we performed a phase 1 dose escalation trial of daily oral nifurtimox with toxicity monitoring to determine the MTD, followed by 3 cycles of nifurtimox in combination with cyclophosphamide and topotecan. Samples were collected to determine the pharmacokinetic parameters maximum concentration, time at which maximum concentration is reached, and area under the curve between 0 and 8 hours. Treatment response was evaluated by radiographic and radionuclide (I-metaiodobenzylguanidine) imaging, measurement of urinary catecholamines, and clearance of bone marrow disease. We determined the MTD of nifurtimox to be 30 mg/kg/d. The non-dose-limiting toxicities were mainly nausea and neuropathy. The dose-limiting toxicities of 2 patients at 40 mg/kg/d were a grade 3 pulmonary hemorrhage and a grade 3 neuropathy (reversible). Overall, nifurtimox was well tolerated by pediatric patients at a dose of 30 mg/kg/d, and tumor responses were seen both as a single agent and in combination with chemotherapy. A Phase 2 study to determine the antitumor efficacy of nifurtimox is currently underway.

Pediatric critical care telemedicine in rural underserved emergency departments.

OBJECTIVE: A disparity in access to health care exists between rural and urban areas. Although 21% of children in the United States live in rural areas, only 3% of pediatric intensivists practice in rural areas. In an attempt to address this issue, we implemented a program of pediatric critical care telemedicine consultations in rural emergency departments (EDs) and report our results. PATIENTS AND METHODS: A prospective evaluation of pediatric critical care consultations in rural EDs was undertaken March 2006 through March 2008. A referral area with a population of 1,000,000 in 19 rural counties in Vermont and upstate New York comprised the study area. MEASUREMENTS AND MAIN RESULTS: Sixty-three telemedicine consultations were performed in 10 rural EDs. The average number of consultations was 6.3 per site (range 2-17). Minor technical issues were identified in 18 consultations (29%). There were 12 primary diagnoses. Telemedicine was used to supervise the critical care transport team on 25 occasions (40%). Consulting intensivists made 236 specific recommendations. Consulting intensivists thought that telemedicine consultations improved patient care 89% of the time, were superior to telephone consultations 91% of the time, and provided good to very good provider-to-provider communications 98% of the time. Referring providers reported that telemedicine consultations improved patient care 88% of the time, were superior to telephone consultations 55% of the time, and provided good to very good communications 94% of the time. CONCLUSIONS: With telemedicine, it is feasible to provide urgent subspecialty critical care for children in underserved rural EDs, improve patient care, and provide a high degree of provider satisfaction. Pediatric critical care telemedicine may help to address the disparities in the access to and the outcome of medical care between rural and urban areas.

Speeds associated with skiing and snowboarding.

BACKGROUND/OBJECTIVE: Traumatic brain injury (TBI) is an important cause of morbidity and mortality in skiing and snowboarding. Although previous studies have advocated the use of a helmet to reduce the incidence of TBI, only a minority of skiers and snowboarders wear helmets. The low use of helmets may be partially due to controversy regarding their effectiveness in a high-speed crash. The protective effect of a ski helmet is diminished at the high speeds a skier or snowboarder can potentially obtain on an open slope. However, ski areas have undergone significant changes in the past decade. Many skiers and snowboarders frequent nontraditional terrain such as gladed areas and terrain parks. Since these areas contain numerous physical obstacles, we hypothesized that skiers and snowboarders would traverse these areas at speeds slow enough to expect a significant protective effect from a helmet. METHODS: Speed data were obtained via radar analysis of 2 groups of expert level skiers and snowboarders traversing a gladed woods trail and terrain park. RESULTS: A total of 113 observations were recorded. Forty-eight observations were made of 9 skiers and snowboarders in gladed terrain, and 65 observations were conducted of 21 skiers and snowboarders in the terrain park. In 79% of the cases in gladed terrain and 94% of the instances in the terrain park, observed speeds were less than 15 mph. CONCLUSIONS: Skiers and snowboarders navigate nontraditional terrain at speeds slower than on open slopes. At the observed velocities, a helmet would be expected to provide significant help in diminishing the occurrence of TBI. Medical authorities should advocate the use of helmets as an important component of an overall strategy to reduce the incidence of TBI associated with skiing and snowboarding.

Changing epidemiology of life-threatening upper airway infections: the reemergence of bacterial tracheitis.

OBJECTIVE: As a consequence of evolving medical practice, the epidemiology of potentially life-threatening upper airway infections is changing. We report our experience over 9 years with viral croup, epiglottitis, and bacterial tracheitis. PATIENTS AND METHODS: We studied a retrospective case series of patients admitted to Vermont Children's Hospital with potentially life-threatening upper airway infections viral croup, epiglottitis, or bacterial tracheitis between 1997 and 2006. MEASUREMENT AND MAIN RESULTS: There were 107 patients with viral croup admitted to Vermont Children's Hospital, with 16 (15%) admitted to the pediatric intensive care unit. Three patients with croup (17% of pediatric intensive care unit admissions, 3% of total admissions) required intubation. There were no serious complications. Eighteen patients were admitted with bacterial tracheitis. Ninety-four percent (n = 17) were admitted to the pediatric intensive care unit. Eighty-three percent (n = 15) were intubated. Twenty-eight percent of patients (n = 5) developed serious complications. Two adolescent patients were admitted with epiglottitis. Both were intubated and recovered without complications. Of 35 patients admitted to the pediatric intensive care unit with these potentially life-threatening upper airway infections, 20 patients (57%) developed respiratory failure. Fifteen patients (75%) had bacterial tracheitis, 3 patients (15%) had viral croup, and 2 patients (10%) had nonclassic epiglottitis. CONCLUSIONS: Immunization against Haemophilus influenza type b and widespread use of corticosteroids for the treatment of viral croup have changed the epidemiology of acute infectious upper airway disease. As potentially life-threatening infections, viral croup and epiglottitis have been eclipsed by bacterial tracheitis. In this series, bacterial tracheitis was 3 times more likely to have caused respiratory failure than viral croup and epiglottitis combined. Bacterial tracheitis should be considered in children who present with acute life-threatening upper airway infection.