Search

Background Sepsis causes death and morbidity in young infants. Globally, an estimated 1.3 – 3.9 million young infants experience sepsis and 400,000 – 700,000 die from sepsis-related conditions annually. Even though there have been significant progress over the past twenty years in reducing young infant mortality, sepsis currently accounts for up to 15% of all young infant deaths. A thorough understanding of young infant sepsis can inform strategies that span prevention, diagnosis and intervention for young infant sepsis. Objectives We aimed to perform a systematic review and meta-analysis to investigate the case fatality rates (CFRs) among young infants less than 90 days with sepsis globally. Methods We used the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2009 guidelines. We searched PubMed, Cochrane Central, Embase and Web of Science for randomized clinical trials and observational studies in English language, published between 2010 to 2019. Studies involving young infants less than 90 days old with sepsis and reported CFRs were included. We obtained pooled CFRs estimates using the random effects model. Additional stratifications by gestation, birth weight, onset of sepsis (early onset was defined as Results Among 6314 articles screened, 240 studies with a total of 437,796 patients met the inclusion criteria and were included in our analysis. 99 came from high income countries, 44 from upper middle income countries, 82 from lower middle income countries, 6 from low income countries and 9 were conducted in multiple countries. Overall, the pooled CFR was 0.18 (95% CI, 0.17–0.19). The CFR was the highest in low income countries (0.25 [95% CI, 0.07–0.43]), followed by lower middle (0.24 [95% CI, 0.21–0.26]), upper middle (0.21 [95% CI, 0.18–0.24]) and lastly high income countries (0.12 [95% CI, 0.11–0.13]). Other factors associated with higher CFRs included prematurity (0.23 [95% CI, 0.19–0.26] vs term CFR 0.10 [95% CI, 0.08–0.13]), low birth weight (0.21 [95% CI, 0.19–0.24] vs normal birth weight 0.19 [95% CI, 0.18–0.20]), early onset sepsis (0.20 [95% CI, 0.17–0.24] vs combined (0.16 [95% CI, 0.14–0.18]) and hospital acquired infection (0.23 [95% CI, 0.17–0.30] vs community acquired infections 0.21 [95% CI, 0.10–0.33]). Time trend analysis showed higher CFRs in the low income countries than the middle and high income countries. A decreasing trend in CFRs over time was observed in high and upper middle income countries, as compared to an increasing trend in lower middle and low income countries. Conclusions While we saw a declining trend of young infant sepsis CFRs among high and upper middle income countries across the years, the increasing trend amongst lower middle and low income countries highlights a disparity in infant sepsis outcomes based on resource availability. We highlight specific vulnerable patient populations that should be further studied in order to reduce the global burden of young infant sepsis.

IntroductionThe effect of neonatal sepsis on the developing brain is not well documented. We aim to perform evidence synthesis to determine the outcome of neurodevelopmental impairment and intellectual disability among survivors of neonatal sepsis. The data gathered will inform on the long-term neurocognitive outcomes of neonates with sepsis and the measures used to document their developmental disability.Methods and analysisWe will perform a search based on the following parameters: neonates and infants less than 90 days old diagnosed with sepsis who had neurocognitive outcomes or measures of developmental disability reported. We will search PubMed, Cochrane Central, Embase and Web of Science for articles in English language published between January 2010 and December 2019. Clinical trials and observational studies will be included. Two independent reviewers will screen studies for eligibility. Data extraction will then be performed using a standardised form. The quality of evidence and risk of bias will be assessed using Cochrane Collaboration’s tool and Risk of Bias in Non-randomised Studies of Intervention (ROBINS-I). The results will be synthesised qualitatively and pooled for meta-analysis.Ethics and disseminationNo formal ethical approval is required as there is no collection of primary data. This systematic review and meta-analysis will be disseminated through conference meetings and peer-reviewed publications.PROSPERO registration numberRegistration submitted CRD42020164334

IMPORTANCE: The global patterns and distribution of case-fatality rates (CFRs) in pediatric severe sepsis and septic shock remain poorly described. OBJECTIVE: We performed a systematic review and meta-analysis of studies of children with severe sepsis and septic shock to elucidate the patterns of CFRs in developing and developed countries over time. We also described factors associated with CFRs. DATA SOURCES: We searched PubMed, Web of Science, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Central systematically for randomized clinical trials and prospective observational studies from earliest publication until January 2017, using the keywords “pediatric,” “sepsis,” “septic shock,” and “mortality.” STUDY SELECTION: Studies involving children with severe sepsis and septic shock that reported CFRs were included. Retrospective studies and studies including only neonates were excluded. DATA EXTRACTION AND SYNTHESIS: We conducted our systematic review and meta-analysis in close accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled case-fatality estimates were obtained using random-effects meta-analysis. The associations of study period, study design, sepsis severity, age, and continents in which studies occurred were assessed with meta-regression. MAIN OUTCOMES AND MEASURES: Meta-analyses to provide pooled estimates of CFR of pediatric severe sepsis and septic shock over time. RESULTS: Ninety-four studies that included 7561 patients were included. Pooled CFRs were higher in developing countries (31.7% [95% CI, 27.3%-36.4%]) than in developed countries (19.3% [95% CI, 16.4%-22.7%]; P

IntroductionNeonatal sepsis has a high mortality rate that varies across different populations. We aim to perform a contemporary global evidence synthesis to determine the case fatality rates of neonatal sepsis, in order to better delineate this public health urgency and inform strategies to reduce fatality in this high-risk population.Methods and analysisWe will search PubMed, Cochrane Central, Embase and Web of Science for articles in English language published between January 2010 and December 2019. All clinical trials and observational studies involving infants less than 90 days old with a clinical diagnosis of sepsis and reported case fatality rate will be included. Two independent reviewers will screen the studies and extract data on study variables chosen a priori. Quality of evidence and risk of bias will be assessed using Cochrane Collaboration’s tool and ROBINS-I. Results will be synthesised qualitatively and pooled for meta-analysis.Ethics and disseminationNo formal ethical approval is required as there is no collection of primary data. This systematic review and meta-analysis will be disseminated through conference meetings and peer-reviewed publications.PROSPERO registration numberCRD42020164321.

The review aims to elucidate the potential of microglia as a therapeutic target in alleviating Alzheimer's Disease (AD). Microglia are the resident immune cells in the brain which respond to the presence of the hallmarks of AD, amyloid-beta (A beta) plaques and neurofibrillary tangles (NFT). Activated microglia are able to phagocytose and secrete pro-inflammatory and anti-inflammatory cytokines. However, the eventual accumulation of excess A beta peptides and NFT in AD means that microglial clearance of pathogens has been impaired. Pro-inflammatory cytokines may also contribute to the neurodegeneration. Based on the amyloid cascade hypothesis, A beta-activated microglia can produce pro-inflammatory cytokines which may exacerbate the hyperphosporylation of tau proteins that forms NFT in AD pathology. Microglial activation can thus be manipulated to prevent neurodegeneration and promote neuroprotection through several therapeutic agents and methods. Further studies regarding comprehensive microglial response towards A beta and NFT are required to develop an effective treatment of AD involving microglia.