The burden and risks of pediatric pneumonia in Nigeria: A desk‐based review of existing literature and data

Background: Pneumonia is a leading killer of children under‐5 years, with a high burden in Nigeria. We aimed to quantify the regional burden and risks of pediatric pneumonia in Nigeria, and specifically the states of Lagos and Jigawa. / Methods: We conducted a scoping literature search for studies of pneumonia morbidity and mortality in under‐5 children in Nigeria from 10th December 2018 to 26th April 2019, searching: Cochrane, PubMed, and Web of Science. We included grey literature from stakeholders' websites and information shared by organizations working in Nigeria. We conducted multivariable logistic regression using the 2016 to 2017 Multiple Cluster Indicators Survey data set to explore factors associated with pneumonia. Descriptive analyses of datasets from 2010 to 2019 was done to estimate trends in mortality, morbidity, and vaccination coverage. / Results: We identified 25 relevant papers (10 from Jigawa, 8 from Lagos, and 14 national data). None included data on pneumonia or acute respiratory tract infection burden in the health system, inpatient case‐fatality rates, severity, or age‐specific pneumonia mortality rates at state level. Secondary data analysis found that no household or caregiver socioeconomic indicators were consistently associated with self‐reported symptoms of cough and/or difficulty breathing, and seasonality was inconsistently associated, dependant on region. / Conclusion: There is a clear evidence gap around the burden of pediatric pneumonia in Nigeria, and challenges with the interpretation of existing household survey data. Improved survey approaches are needed to understand the risks of pediatric pneumonia in Nigeria, alongside the need for investment in reliable routine data systems to provide data on the clinical pneumonia burden in Nigeria

Health system challenges for improved childhood pneumonia case management in Lagos and Jigawa, Nigeria

Background: Case fatality rates for childhood pneumonia in Nigeria remain high. There is a clear need for improved case management of pneumonia, through the sustainable implementation of the Integrated Management of Childhood Illnesses (IMCI) diagnostic and treatment algorithms. We explored barriers and opportunities for improved case management of childhood pneumonia in Lagos and Jigawa states, Nigeria. / Methods: A mixed‐method analysis was conducted to assess the current health system capacity to deliver quality care. This was done through audits of 16 facilities in Jigawa and 14 facilities in Lagos, questionnaires (n = 164) and 13 focus group discussions with providers. Field observations provided context for data analysis and triangulation. / Results: There were more private providers in Lagos (4/8 secondary facilities) and more government providers in Jigawa (4/8 primary, 3/3 secondary, and 1/1 tertiary facilities). Oxygen and pulse oximeters were available in two of three in Jigawa and six of eight in Lagos of the sampled secondary care facilities. None of the eight primary facilities surveyed in Jigawa had oxygen or pulse oximetry available while in Lagos two of three primary facilities had oxygen and one of three had pulse oximeters. Other IMCI and emergency equipment were also lacking including respiratory rate timers, particularly in Jigawa state. Health care providers scored poorly on knowledge of IMCI, though previous IMCI training was associated with better knowledge. Key enabling factors in delivering pediatric care highlighted by health care providers included accountability procedures and feedback loops, the provision of free medication for children, and philanthropic acts. Common barriers to provide care included the burden of out‐of‐pocket payments, challenges in effective communication with caregivers, delayed presentation, and lack of clear diagnosis, and case management guidelines. / Conclusion: There is an urgent need to improve how the prevention and treatment of pediatric pneumonia is directed in both Lagos and Jigawa. Priority areas for reducing pediatric pneumonia burden are training and mentoring of health care providers, community health education, and introduction of oximeters and oxygen supply

The role of clathrin in post-golgi trafficking in toxoplasma gondii

Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle

A bibliometric study of the literature on technological innovation: an analysis of 60 international academic journals

This paper aims to contribute to the debate on technological innovation, organization and work. Although technological innovation remained a debated topic in the academic literature during the past years, its implications for organizational processes seem still not sufficiently theorized and empirically investigated. By using two complementary journals’ rankings a search in the ISI Web of Science platform from 1985 through 2013 was performed. To analyze the 998 scientific retrieved contributions a bibliometric analysis has been conducted, adopting also Social Network Analysis tools. Our results reveal a significant growth of the technological innovation literature over the investigated period, the multidisciplinarity of the field and, particularly, the relevance of management and business & economics contributions. Overall, this study offers a broad overview of the literature on technological innovation and emphasizes the opportunity to investigate the role of technological innovation within the organizational life.This paper aims to contribute to the debate on technological innovation, organization and work. Although technological innovation remained a debated topic in the academic literature during the past years, its implications for organizational processes seem still not sufficiently theorized and empirically investigated. By using two complementary journals’ rankings a search in the ISI Web of Science platform from 1985 through 2013 was performed. To analyze the 998 scientific retrieved contributions a bibliometric analysis has been conducted, adopting also Social Network Analysis tools. Our results reveal a significant growth of the technological innovation literature over the investigated period, the multidisciplinarity of the field and, particularly, the relevance of management and business & economics contributions. Overall, this study offers a broad overview of the literature on technological innovation and emphasizes the opportunity to investigate the role of technological innovation within the organizational life.Monograph's chapter

In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression

April 1, 2010Mouse models have markedly improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic experimentation. Here, we report the adaptation of loss-of-function screening to mouse models of cancer. Specifically, we have been able to introduce a library of shRNAs into individual mice using transplantable Eμ-myc lymphoma cells. This approach has allowed us to screen nearly 1,000 genetic alterations in the context of a single tumor-bearing mouse. These experiments have identified a central role for regulators of actin dynamics and cell motility in lymphoma cell homeostasis in vivo. Validation experiments confirmed that these proteins represent bona fide lymphoma drug targets. Additionally, suppression of two of these targets, Rac2 and twinfilin, potentiated the action of the front-line chemotherapeutic vincristine, suggesting a critical relationship between cell motility and tumor relapse in hematopoietic malignancies.National Institutes of Health (U.S.) (RO1 CA128803-01)Massachusetts Institute of Technology. Dept. of Biology (Training Grant)Massachusetts Institute of Technology. Undergraduate Research Opportunities ProgramNational Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant 1-U54-CA112967

Microanatomy of Adult Zebrafish Extraocular Muscles

Binocular vision requires intricate control of eye movement to align overlapping visual fields for fusion in the visual cortex, and each eye is controlled by 6 extraocular muscles (EOMs). Disorders of EOMs are an important cause of symptomatic vision loss. Importantly, EOMs represent specialized skeletal muscles with distinct gene expression profile and susceptibility to neuromuscular disorders. We aim to investigate and describe the anatomy of adult zebrafish extraocular muscles (EOMs) to enable comparison with human EOM anatomy and facilitate the use of zebrafish as a model for EOM research. Using differential interference contrast (DIC), epifluorescence microscopy, and precise sectioning techniques, we evaluate the anatomy of zebrafish EOM origin, muscle course, and insertion on the eye. Immunofluorescence is used to identify components of tendons, basement membrane and neuromuscular junctions (NMJs), and to analyze myofiber characteristics. We find that adult zebrafish EOM insertions on the globe parallel the organization of human EOMs, including the close proximity of specific EOM insertions to one another. However, analysis of EOM origins reveals important differences between human and zebrafish, such as the common rostral origin of both oblique muscles and the caudal origin of the lateral rectus muscles. Thrombospondin 4 marks the EOM tendons in regions that are highly innervated, and laminin marks the basement membrane, enabling evaluation of myofiber size and distribution. The NMJs appear to include both en plaque and en grappe synapses, while NMJ density is much higher in EOMs than in somatic muscles. In conclusion, zebrafish and human EOM anatomy are generally homologous, supporting the use of zebrafish for studying EOM biology. However, anatomic differences exist, revealing divergent evolutionary pressures

Remdesivir for the Treatment of Covid-19 — Preliminary Report

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705. opens in new tab.

Pharmacodynamic evaluation of commonly prescribed oral antibiotics against respiratory bacterial pathogens

<p>Abstract</p> <p>Background</p> <p>Upper and lower respiratory tract infections (RTIs) account for a substantial portion of outpatient antibiotic utilization. However, the pharmacodynamic activity of commonly used oral antibiotic regimens has not been studied against clinically relevant pathogens. The objective of this study was to assess the probability of achieving the requisite pharmacodynamic exposure for oral antibacterial regimens commonly prescribed for RTIs in adults against bacterial isolates frequently involved in these processes (<it>S. pneumoniae</it>, <it>H. influenzae</it>, and <it>M. catharralis</it>).</p> <p>Methods</p> <p>Using a 5000-subject Monte Carlo simulation, the cumulative fractions of response (CFR), (i.e., probabilities of achieving requisite pharmacodynamic targets) for the most commonly prescribed oral antibiotic regimens, as determined by a structured survey of medical prescription patterns, were assessed against local respiratory bacterial isolates from adults in São Paulo collected during the same time period. Minimal inhibitory concentration (MIC) of 230 isolates of <it>Streptococcus pneumoniae </it>(103), <it>Haemophilus influenzae </it>(98), and <it>Moraxella catharralis </it>(29) from a previous local surveillance were used.</p> <p>Results</p> <p>The most commonly prescribed antibiotic regimens were azithromycin 500 mg QD, amoxicillin 500 mg TID, and levofloxacin 500 mg QD, accounting for 58% of the prescriptions. Varied doses of these agents, plus gatifloxacin, amoxicillin-clavulanate, moxifloxacin, and cefaclor made up the remaining regimens. Utilizing aggressive pharmacodynamic exposure targets, the only regimens to achieve greater than 90% CFR against all three pathogens were amoxicillin/amoxicillin-clavulanate 500 mg TID (> 91%), gatifloxacin 400 mg QD (100%), and moxifloxacin 400 mg QD (100%). Considering <it>S. pneumoniae </it>isolates alone, azithromycin 1000 mg QD also achieved greater than 90% CFR (91.3%).</p> <p>Conclusions</p> <p>The only regimens to achieve high CFR against all three pathogen populations in both scenarios were gatifloxacin 400 mg QD, moxifloxacin 400 mg QD, and amoxicillin-clavulanate 500 mg TID. These data suggest the need for reconsideration of empiric antibiotic regimen selection among adult patients with RTIs in the São Paulo area. Additionally, this type of study could be used to optimize prescribing patterns in specific regions in light of emerging resistance.</p