Pediatric Emergency Care Research Networks: A Research Agenda

BackgroundPediatric emergency care research networks have evolved substantially over the past two decades. Some networks are specialized in specific areas (e.g., sedation, simulation) while others study a variety of medical and traumatic conditions. Given the increased collaboration between pediatric emergency research networks, the logical next step is the development of a research priorities agenda to guide global research in emergency medical services for children (EMSC).ObjectivesAn international group of pediatric emergency network research leaders was assembled to develop a list of research priorities for future collaborative endeavors within and between pediatric emergency research networks.MethodsBefore an in‐person meeting, we used a modified Delphi approach to achieve consensus around pediatric emergency research network topic priorities. Further discussions took place on May 15, 2018, in Indianapolis, Indiana, at the Academic Emergency Medicine (AEM) consensus conference “Aligning the Pediatric Emergency Medicine Research Agenda to Reduce Health Outcome Gaps.” Here, a group of 40 organizers and participants met in a 90‐minute “breakout” session to review and further develop the initial priorities.ResultsWe reached consensus on five clinical research priorities that would benefit from collaboration among the existing and future emergency networks focused on EMSC: sepsis, trauma, respiratory conditions, pharmacology of emergency conditions, and mental health emergencies. Furthermore, we identified nonclinical research priorities categorized under the domains of technology, knowledge translation, and organization/administration of pediatric emergency care.ConclusionThe identification of pediatric emergency care network research priorities within the domains of clinical care, technology, knowledge translation and organization/administration of EMSC will facilitate and help focus collaborative research within and among research networks globally. Engagement of essential stakeholders including EMSC researchers, policy makers, patients, and their caregivers will stimulate advances in the delivery of emergency care to children around the globe.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147119/1/acem13656.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147119/2/acem13656_am.pd

Experience and Challenges from Clinical Trials with Malaria Vaccines in Africa.

Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available.African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need.However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained

Mirror, mirror on the wall: which microbiomes will help heal them all?

BACKGROUND: Clinicians have known for centuries that there is substantial variability between patients in their response to medications—some individuals exhibit a miraculous recovery while others fail to respond at all. Still others experience dangerous side effects. The hunt for the factors responsible for this variation has been aided by the ability to sequence the human genome, but this just provides part of the picture. Here, we discuss the emerging field of study focused on the human microbiome and how it may help to better predict drug response and improve the treatment of human disease. DISCUSSION: Various clinical disciplines characterize drug response using either continuous or categorical descriptors that are then correlated to environmental and genetic risk factors. However, these approaches typically ignore the microbiome, which can directly metabolize drugs into downstream metabolites with altered activity, clearance, and/or toxicity. Variations in the ability of each individual’s microbiome to metabolize drugs may be an underappreciated source of differences in clinical response. Complementary studies in humans and animal models are necessary to elucidate the mechanisms responsible and to test the feasibility of identifying microbiome-based biomarkers of treatment outcomes. SUMMARY: We propose that the predictive power of genetic testing could be improved by taking a more comprehensive view of human genetics that encompasses our human and microbial genomes. Furthermore, unlike the human genome, the microbiome is rapidly altered by diet, pharmaceuticals, and other interventions, providing the potential to improve patient care by re-shaping our associated microbial communities

Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions

BACKGROUND: To assess the performance of Candida albicans germ tube antibody (CAGTA), (1 → 3)-ß-D-glucan (BDG), mannan antigen (mannan-Ag), anti-mannan antibodies (mannan-Ab), and Candida DNA for diagnosing invasive candidiasis (IC) in ICU patients with severe abdominal conditions (SAC). METHODS: A prospective study of 233 non-neutropenic patients with SAC on ICU admission and expected stay ≥ 7 days. CAGTA (cutoff positivity ≥ 1/160), BDG (≥80, 100 and 200 pg/mL), mannan-Ag (≥60 pg/mL), mannan-Ab (≥10 UA/mL) were measured twice a week, and Candida DNA only in patients treated with systemic antifungals. IC diagnosis required positivities of two biomarkers in a single sample or positivities of any biomarker in two consecutive samples. Patients were classified as neither colonized nor infected (n = 48), Candida spp. colonization (n = 154) (low-grade, n = 130; high-grade, n = 24), and IC (n = 31) (intra-abdominal candidiasis, n = 20; candidemia, n = 11). RESULTS: The combination of CAGTA and BDG positivities in a single sample or at least one of the two biomarkers positive in two consecutive samples showed 90.3 % (95 % CI 74.2–98.0) sensitivity, 42.1 % (95 % CI 35.2–98.8) specificity, and 96.6 % (95 % CI 90.5–98.8) negative predictive value. BDG positivities in two consecutive samples had 76.7 % (95 % CI 57.7–90.1) sensitivity and 57.2 % (95 % CI 49.9–64.3) specificity. Mannan-Ag, mannan-Ab, and Candida DNA individually or combined showed a low discriminating capacity. CONCLUSIONS: Positive Candida albicans germ tube antibody and (1 → 3)-ß-D-glucan in a single blood sample or (1 → 3)-ß-D-glucan positivity in two consecutive blood samples allowed discriminating invasive candidiasis from Candida spp. colonization in critically ill patients with severe abdominal conditions. These findings may be helpful to tailor empirical antifungal therapy in this patient population

Solutions of polysaccharides in N-methyl morpholine N-oxide (MMNO)

International audienc

Solubilization of cellulose and other plant structural polysaccharides in 4-methylmorpholine N-oxide: an improved method for the study of cell-wall constituents.

International audienc

Possible role of specific immunoglobulin M antibodies to Plasmodium falciparum antigens in immunoprotection of humans living in a hyperendemic area, Burkina Faso.

Two seroepidemiological studies were performed in an area of Burkina Faso hyperendemic for malaria to estimate the protective role of immunoglobulin M (IgM) antibodies. Six cross-sectional surveys were carried out on children (ages, < 16 years) in the village of Karankasso. The evolution of antibodies to crude extracts of Plasmodium falciparum (IgG or IgM antisomatic and IgG antiexoantigens) were tested by IFI or enzyme-linked immunosorbent assay and were followed up according to the fluctuations of the parasite densities. Specific IgG antibodies had the same evolution as parasite densities. By contrast, specific IgM antibodies increased when IgG and parasite densities began to decrease (despite a high inoculation rate). A longitudinal survey of 77 children and adults was conducted in another village (Dafinso). In that study, clinical follow-up of the selected individuals allowed us to define three groups in the population. Children in group 1 were considered nonimmune (children with one or more malaria attacks). Group 2 was composed of semiimmune children who did not present with any malarial attack during the survey but who had high levels of parasitemia during the transmission period. Group 3 was composed of immunoprotected adults. Specific IgM and IgG antibodies to crude extracts or a recombinant antigen (glutamate-rich protein) of P. falciparum were tested. Specific IgM antibodies were lower in group 1 (nonimmune) than in groups 2 (semiimmune) and 3 (immunoprotected). Furthermore, there was a negative correlation between parasite densities and the levels of specific IgM antibodies. We discuss the possible role of IgM antibodies in the acquisition of immunity to malaria