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 < .001). Meta-analysis of CFRs also showed significant heterogeneity across studies. Continents that include mainly developing countries reported higher CFRs (adjusted odds ratios: Africa, 7.89 [95% CI, 6.02-10.32]; P < .001; Asia, 3.81 [95% CI, 3.60-4.03]; P < .001; South America, 2.91 [95% CI, 2.71-3.12]; P < .001) than North America. Septic shock was associated with higher CFRs than severe sepsis (adjusted odds ratios, 1.47 [95% CI, 1.41-1.54]). Younger age was also a risk factor (adjusted odds ratio, 0.95 [95% CI, 0.94-0.96] per year of increase in age). Earlier study eras were associated with higher CFRs (adjusted odds ratios for 1991-2000, 1.24 [95% CI, 1.13-1.37]; P < .001) compared with 2011 to 2016. Time-trend analysis showed higher CFRs over time in developing countries than developed countries. CONCLUSIONS AND RELEVANCE Despite the declining trend of pediatric severe sepsis and septic shock CFRs, the disparity between developing and developed countries persists. Further characterizations of vulnerable populations and collaborations between developed and developing countries are warranted to reduce the burden of pediatric sepsis globally.

The grouper, Epinephelus lanceolatus, is a vulnerable species of high economic value. An effective protocol was developed for the cryopreservation of E. lanceolatus by comparing different extenders produced by mixing various cryoprotectants (dimethyl sulfoxide, methanol and glycerol) and diluents (MPRS, TS-2, TS-19, Cortland and Hank's). Using computer-assisted sperm analysis (CASA) and morphological analysis, the sperm motility and fertilization rates from postthaw sperm were comparable to untreated controls. The results revealed that MPRS (containing 12% DMSO) or TS-19 (containing 12% DMSO), were the optimum extenders for protecting the sperm from cryo-damage in liquid nitrogen. The post-thaw sperm maintained high motility (90.61 AE 3.03%) and a fertilization rate (92.27 AE 2.43%) similar (P > 0.05) to fresh sperm (94.34 AE 4% and 94.10 AE 1.87%). This study is the first to report on the successful sperm cryopreservation of E. lanceolatus and provides an important tool for repopulating this species through aquaculture.During the spawning season from the end of April to mid-October 2009, gametes of E. lanceolatus were collected from *These authors contributed equally to this work. U.S.

ObjectiveCurrent knowledge on the global burden of infant sepsis is limited to population-level data. We aimed to summarize global case fatality rates (CFRs) of young infants with sepsis, stratified by gross national income (GNI) status and patient-level risk factors.MethodsWe performed a systematic review and meta-analysis on CFRs among young infants &lt; 90 days with sepsis. We searched PubMed, Cochrane Central, Embase, and Web of Science for studies published between January 2010 and September 2019. We obtained pooled CFRs estimates using the random effects model. We performed a univariate analysis at patient-level and a meta-regression to study the associations of gestational age, birth weight, onset of sepsis, GNI, age group and culture-proven sepsis with CFRs.ResultsThe search yielded 6314 publications, of which 240 studies (N = 437,796 patients) from 77 countries were included. Of 240 studies, 99 were conducted in high-income countries, 44 in upper-middle-income countries, 82 in lower-middle-income countries, 6 in low-income countries and 9 in multiple income-level countries. Overall pooled CFR was 18% (95% CI, 17–19%). The CFR was highest for low-income countries [25% (95% CI, 7–43%)], followed by lower-middle [25% (95% CI, 7–43%)], upper-middle [21% (95% CI, 18–24%)] and lowest for high-income countries [12% (95% CI, 11–13%)]. Factors associated with high CFRs included prematurity, low birth weight, age less than 28 days, early onset sepsis, hospital acquired infections and sepsis in middle- and low-income countries. Study setting in middle-income countries was an independent predictor of high CFRs. We found a widening disparity in CFRs between countries of different GNI over time.ConclusionYoung infant sepsis remains a major global health challenge. The widening disparity in young infant sepsis CFRs between GNI groups underscore the need to channel greater resources especially to the lower income regions.Systematic Review Registration[www.crd.york.ac.uk/prospero], identifier [CRD42020164321].

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

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.

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