Publications by authors named "Madrid L"

Background: It is crucial to consider cultural, religious, and socio-behavioural factors that may influence the acceptability of Minimally Invasive Tissues Sampling (MITS). MITS is being used to understand the causes of child death and conducted in nine countries within Africa and South Asia with the highest child mortality. Progress has been made in the development of laboratory infrastructures and training for physicians to do MITS, but many communities are concerned about the religious acceptability of taking samples from deceased children.

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Introduction: Malnutrition contributes to 45% of all childhood deaths globally, but these modelled estimates lack direct measurements in countries with high malnutrition and under-5 mortality rates. We investigated malnutrition's role in infant and child deaths in the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

Methods: We analysed CHAMPS data from seven sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone and South Africa) collected between 2016 and 2023.

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Article Synopsis
  • The study investigates the role of meningitis in child mortality under five years old, particularly focusing on data from six sub-Saharan African countries and Bangladesh.
  • It employs post-mortem minimally invasive tissue sampling (MITS) to identify the causes of death and pathogens responsible for meningitis in this age group from December 2016 to December 2023.
  • Findings reveal that meningitis contributed to 7% of child deaths, with common pathogens identified being Acinetobacter baumannii and Klebsiella pneumoniae, particularly affecting neonates and infants.
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Transfection efficiency is a critical parameter in gene therapy and molecular biology, representing the success rate at which nucleic acids are introduced and expressed in target cells. The combination of aptamers with nanotechnology-based delivery systems has demonstrated remarkable improvements in the transfection efficiency of therapeutic agents and holds significant potential for advancing gene therapy and the development of targeted treatments for various diseases, including cancer. In this work, cationic carbosilane dendritic systems are presented as an alternative to commercial transfection agents, demonstrating an increase in transfection efficiency when used for the internalization of apMNKQ2, an aptamer selected against a target in cancer.

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Importance: The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies.

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In resource-limited settings where vital registration and medical death certificates are unavailable or incomplete, verbal autopsy (VA) is often used to attribute causes of death (CoD) and prioritize resource allocation and interventions. We aimed to determine the CoD concordance between InterVA and CHAMPS's method. The causes of death (CoDs) of children <5 were determined by two methods using data from seven low- and middle-income countries (LMICs) enrolled in the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

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Introduction: Determining aetiology of severe illness can be difficult, especially in settings with limited diagnostic resources, yet critical for providing life-saving care. Our objective was to describe the accuracy of antemortem clinical diagnoses in young children in high-mortality settings, compared with results of specific postmortem diagnoses obtained from Child Health and Mortality Prevention Surveillance (CHAMPS).

Methods: We analysed data collected during 2016-2022 from seven sites in Africa and South Asia.

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We have recently witnessed that considerable progresses have been made in the rapid detection and appropriate treatments of COVID-19, but still this virus remains one of the main targets of world research. Based on the knowledge of the complex mechanism of viral infection we designed peptide-dendrimer inhibitors of SARS-CoV-2with the aim to block cell infection through interfering with the host-pathogen interactions. We used two different strategies: i) the first one aims at hindering the virus anchorage to the human cell; ii) the second -strategy points to interfere with the mechanism of virus-cell membrane fusion.

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Background: People who inject drugs (PWID) experience many health problems which result in a heavy economic and public health burden. To tackle this issue, France opened two drug consumption rooms (DCRs) in Paris and Strasbourg in 2016. This study assessed their long-term health benefits, costs and cost-effectiveness.

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Article Synopsis
  • - The study focused on how well doctors' pre-death diagnoses match up with findings from autopsies for children under five who died in Ethiopia, specifically looking at lung issues.
  • - Out of 75 cases reviewed, only 52% were accurately diagnosed before death, with a significant 35% discrepancy rate between antemortem and postmortem diagnoses.
  • - Major reasons for misdiagnoses were identified as lack of knowledge and poor teamwork among healthcare providers, emphasizing the need for better education and collaboration to improve diagnostic accuracy.
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This study reports the preliminary efficacy of an innovative school-based, technology-enhanced social-emotional learning program called "mindfulness-based collaborative social reasoning" (MBCSR) for middle school students. MBCSR was developed by an interdisciplinary team of educational psychologists, mindfulness researchers, computer scientists, and health experts. We integrated the strengths of contemplative approaches, collaborative small group discussions, learning technology, and multidimensional assessments of students' social-emotional outcomes.

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Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS).

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Background: Malaria is a leading cause of childhood mortality worldwide. However, accurate estimates of malaria prevalence and causality among patients who die at the country level are lacking due to the limited specificity of diagnostic tools used to attribute etiologies. Accurate estimates are crucial for prioritizing interventions and resources aimed at reducing malaria-related mortality.

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Article Synopsis
  • The CHAMPS Network investigates childhood deaths, focusing on pneumonia's role and the pathogens involved in cases from six sub-Saharan African countries and Bangladesh from December 2016 to December 2022.
  • Out of 1,120 deaths analyzed, pneumonia was identified as a contributing factor in 40.6%, with most victims being around 9 months old, and 82.9% of these cases had identifiable pathogens.
  • Among the pneumonia deaths, community-acquired pneumonia was responsible for 67.3%, with leading pathogens including Streptococcus pneumoniae and Klebsiella pneumoniae, while 32.7% were linked to hospital-acquired pneumonia.
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Background: Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings.

Methods: We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021.

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Cholinergic signaling plays a crucial role in the regulation of adult hippocampal neurogenesis; however, the mechanisms by which acetylcholine mediates neurogenic effects are not completely understood. Here, we report the expression of muscarinic acetylcholine receptor subtype M4 (M4 mAChR) on a subpopulation of neural precursor cells (NPCs) in the adult mouse hippocampus, and demonstrate that its pharmacological stimulation promotes their proliferation, thereby enhancing the production of new neurons in vivo. Using a targeted ablation approach, we also show that medial septum (MS) and the diagonal band of Broca (DBB) cholinergic neurons support both the survival and morphological maturation of adult-born neurons in the mouse hippocampus.

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Background: We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin.

Methods: Infants with HIV aged 1-12 months, weighing ≥3 kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD).

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Article Synopsis
  • Optimal antituberculosis therapy is crucial for achieving good health outcomes in patients.
  • Research shows that infants with HIV receiving standard doses of first-line TB drugs have significantly lower peak plasma concentrations than adults.
  • This suggests that increasing the dosage of these TB drugs in infants may be necessary for better treatment effectiveness.
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Background: Most childhood deaths globally are considered preventable through high-quality clinical care, which includes adherence to clinical care recommendations. Our objective was to describe adherence to World Health Organization recommendations for the management of leading causes of death among children.

Methods: We conducted a retrospective, descriptive study examining clinical data for children aged 1-59 months who were hospitalized and died in a Child Health and Mortality Prevention Surveillance (CHAMPS) catchment, December 2016-June 2021.

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Article Synopsis
  • Invasive Group B Streptococcus (GBS) is a major factor in early-onset neonatal sepsis and stillbirth, which this study evaluated in seven low- and middle-income countries to determine its impact on infant mortality.
  • The research included the analysis of 2,966 deaths from December 2016 to December 2021 using minimally invasive tissue sampling, identifying GBS as a contributing factor in 2.7% of infant deaths, including 2.3% of stillborn cases.
  • Results showed significant variation in GBS-attributed deaths across countries, particularly affecting low-birth-weight infants, highlighting the need for tailored interventions in different regions to address this issue.
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Importance: The number of deaths of children younger than 5 years has been steadily decreasing worldwide, from more than 17 million annual deaths in the 1970s to an estimated 5.3 million in 2019 (with 2.8 million deaths occurring in those aged 1-59 months [53% of all deaths in children aged <5 years]).

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Background: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa.

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Background: Child mortality is high in Ethiopia, but reliable data on the causes of death are scarce. We aimed to gather data for the contributory causes of stillbirth and child deaths in eastern Ethiopia.

Methods: In this population-based post-mortem study, we established a death-notification system in health facilities and in the community in Kersa (rural), Haramaya (rural) and Harar (urban) in eastern Ethiopia, at a new site of the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

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Background: Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia.

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Pneumonia is a leading cause of child mortality. However, currently we lack simple, objective, and accurate risk-stratification tools for pediatric pneumonia. Here we test the hypothesis that measuring biomarkers of immune and endothelial activation in children with pneumonia may facilitate the identification of those at risk of death.

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