To synthesize the available evidence examining the efficacy and safety of levetiracetam compared with phenytoin or fosphenytoin in benzodiazepine-refractory pediatric status epilepticus. DATA SOURCES:We searched (from inception until April 27, 2020) Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials.STUDY SELECTION: Two reviewers, independently and in duplicate, screened citations and manuscripts for eligible randomized controlled trials. DATA EXTRACTION AND SYNTHESIS:Independently and in duplicate, we performed data abstraction, risk of bias assessment, and certainty assessment using Grading of Recommendations, Assessment, Development, and Evaluation. We performed meta-analyses using randomeffect models or, if insufficient data, presented findings narratively. RESULTS:We identified seven randomized controlled trials (n = 1,575). Pooled analysis demonstrated low certainty evidence for no difference of levetiracetam on time to seizure cessation (mean difference, -3.11 min; 95% CI, -6.67 to 0.45), early seizure cessation (relative risk, 1.09, 95% CI, 0.95-1.26), or late seizure cessation (relative risk, 1.05; 95% CI, 0.93-1.18). Adverse event outcomes were limited by low event numbers. We found low certainty evidence for less respiratory depression with levetiracetam (relative risk, 0.28; 95% CI, 0.12-0.69). CONCLUSIONS:The efficacy of levetiracetam is comparable with phenytoin or fosphenytoin in children with benzodiazepine-refractory status epilepticus (low certainty evidence). Levetiracetam may cause less respiratory depression. Clinicians and guideline developers should weigh safety profiles when choosing between these agents.

Background Sepsis, the dysregulated host response to infection, triggers abnormal pro-coagulant and pro-inflammatory host responses. Limitations in early disease intervention highlight the need for effective diagnostic and prognostic biomarkers. Protein C’s role as an anticoagulant and anti-inflammatory molecule makes it an appealing target for sepsis biomarker studies. This meta-analysis aims to assess the diagnostic and prognostic value of protein C (PC) as a biomarker for adult sepsis. Methods We searched MEDLINE, PubMed, EMBASE, CINAHL and Cochrane Library from database inception to September 12, 2021. We included prospective observational studies of (1) adult patients (> 17) with sepsis or suspicion of sepsis that; (2) measured PC levels with 24 h of study admission with; and (3) the goal of examining PC as a diagnostic or prognostic biomarker. Two authors screened articles and conducted risk of bias (RoB) assessment, using the Quality in Prognosis Studies (QUIPS) and the Quality Assessment in Diagnostic Studies-2 (QUADAS-2) tools. If sufficient data were available, meta-analysis was conducted to estimate the standardized mean difference (SMD) between patient populations. Results Twelve studies were included, and 8 were synthesized for meta-analysis. Pooled analysis demonstrated moderate certainty of evidence that PC levels were less reduced in sepsis survivors compared to non-survivors (6 studies, 741 patients, SMD = 0.52, 95% CI 0.24–0.81, p = 0.0003, I2 = 55%), and low certainty of evidence that PC levels were less reduced in septic patients without disseminated intravascular coagulation (DIC) compared to those with DIC (3 studies, 644 patients, SMD = 0.97, 95% CI 0.62–1.32, p < 0.00001, I2 = 67%). PC could not be evaluated as a diagnostic tool due to heterogeneous control populations between studies. Conclusion and relevance Our review demonstrates that PC levels were significantly higher in sepsis survivors compared to non-survivors and patients with sepsis but not disseminated intravascular coagulation (DIC). Our evaluation is limited by high RoB in included studies and poor reporting of the sensitivity and specificity of PC as a sepsis biomarker. Future studies are needed to determine the sensitivity and specificity of PC to identify its clinical significance as a biomarker for early sepsis recognition. Trial Registration PROSPERO registration number: CRD42021229786. The study protocol was published in BMJ Open.

OBJECTIVE: Evaluating risk for sepsis is complicated due to limited understanding of how social determinants of health (SDoH) influence the occurence of the disease. This scoping review aims to identify gaps and summarize the existing literature on SDoH and the development of sepsis in adults. DATA SOURCES: A literature search using key terms related to sepsis and SDoH was conducted using Medline and PubMed. STUDY SELECTION: Studies were screened by title and abstract and then full text in duplicate. Articles were eligible for inclusion if they: 1) evaluated at least one SDoH on the development of sepsis, 2) participants were 18 years or older, and 3) the studies were written in English between January 1970 and January 2022. Systematic reviews, meta-analyses, editorials, letters, commentaries, and studies with nonhuman participants were excluded. DATA EXTRACTION: Data were extracted in duplicate using a standardized data extraction form. Studies were grouped into five categories according to the SDoH they evaluated (race, socioeconomic status [SES], old age and frailty, health behaviors, and social support). The study characteristics, key outcomes related to incidence of sepsis, mortality, and summary statements were included in tables. DATA SYNTHESIS: The search identified 637 abstracts, 20 of which were included after full-text screening. Studies evaluating SES, old age, frailty, and gender demonstrated an association between sepsis incidence and the SDoH. Studies that examined race demonstrated conflicting conclusions as to whether Black or White patients were at increased risk of sepsis. Overall, a major limitation of this analysis was the methodological heterogeneity between studies. CONCLUSIONS: There is evidence to suggest that SDoH impacts sepsis incidence, particularly SES, gender, old age, and frailty. Future prospective cohort studies that use standardized methods to collect SDoH data, particularly race-based data, are needed to inform public health efforts to reduce the incidence of sepsis and help clinicians identify the populations most at risk.

IntroductionSepsis is a dysregulated host response to infection characterised by activation of proinflammatory and procoagulant mechanisms. Protein C (PC)’s activity as an anticoagulant and antiinflammatory molecule makes it an appealing target for sepsis biomarker studies. To date, there has been no systematic review of PC as a sepsis biomarker.ObjectivesTo evaluate the diagnostic accuracy and prognostic strength of PC as a biomarker for adult sepsis.Methods and analysisMedline, Embase, Cochrane Library, PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be searched from inception through 20 January 2021 for prospective observational studies that evaluate the use of PC as a diagnostic or prognostic biomarker for adult sepsis. Title and abstract screening, full-text screening and data extraction will be conducted in duplicate. Risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies and Quality in Prognostic Studies tools. If sufficient data are available, a meta-analysis will be conducted. The standardised mean difference and 95% CI will be calculated for prognostic and diagnostic studies. If possible, a hierarchical summary receiver operator characteristic curve will be generated to assess overall prognostic and diagnostic biomarker accuracy. I2 statistics will be used to assess heterogeneity. Sensitivity analysis will be performed by removing studies with a high risk of bias and re-examining the meta-analysis results.Ethics and disseminationGiven this is a systematic review and meta-analysis, there is no requirement for ethics approval. Findings will be disseminated through a peer-reviewed publication and social media.PROSPERO registration numberCRD42021229786.