The prognostic utility of protein C as a biomarker for adult sepsis: a systematic review and meta-analysis.

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.

Levetiracetam Versus Phenytoin or Fosphenytoin for Second-Line Treatment of Pediatric Status Epilepticus: A Meta-Analysis.

OBJECTIVE: 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 random-effect 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.

Experiences of a virtual day program for adolescents with eating disorders: a qualitative analysis of benefits and barriers.

BACKGROUND: Throughout the COVID-19 pandemic, there was a detrimental impact to the symptoms and treatment of eating disorders, causing an increase in medical admissions and visits. Day treatment programs (DTPs), often used to bridge the gap between inpatient and outpatient treatment, were converted to online formats. This study aims to explore the impact of the transition to virtual DTPs on eating disorder treatment from the perspective of adolescents, their caregivers, and program staff. METHODS: Twelve participants (3 adolescents, 4 caregivers, 5 healthcare providers) in a virtual day treatment program were interviewed using a semi-structured interview guide. Interviews were transcribed and managed with qualitative software NVivo 11.0. Conventional analysis was used to inductively identify pertinent themes related to patient, caregiver, and healthcare staff perceptions and experiences of the virtual day treatment. Summative content analysis provided counts of the barriers and benefits of virtual day treatment as identified by participants. RESULTS: The majority of participants (10/12) had exposure to both virtual and in person settings, most participants (11/12) felt in-person day programs would be superior to virtual programs. Common limitations of the virtual format were feelings of isolation, less support from healthcare providers, parental burnout, and increased disordered eating. Common benefits were increased accessibility, parental involvement, improved communication with healthcare staff, and the ability for participants to be in their home environment and eat home food. Suggestions for improvement included designing a hybrid model of day treatment, increased family involvement, extending the day program to include dinners with family, and screening for patient appropriateness for the virtual setting. CONCLUSION: This qualitative study suggests that there are many barriers to effective implementation of virtual day programs. However, the virtual DTP program offers increased accessibility to patients during a period of a health pandemic and to patients in rural/remote areas with limited treatment options. Suggestions provided by participants in this study, such as increased family involvement, frequency of in person check-ins and increased number of meals supported by the program, may help to improve outcomes in virtual day treatment programs.

Eating disorders are serious psychiatric conditions that are detrimental to many adolescents and their families. The COVID-19 pandemic exacerbated the impact of eating disorders on adolescents due to social isolation, and increased levels of anxiety and depression. In addition, many of the treatment programs were converted to an online format. Day treatment programs, which normally involve patients spending the day at the hospital and returning home for the evening with their families, were converted to an online format. Although there is a lot of evidence supporting in-person day programs, there is limited research on the perspectives of various stakeholders on virtual programs. The goal of this study was to interview adolescents, caregivers and healthcare staff that had participated in a virtual day treatment program during the pandemic to understand their perspective on the pros and cons of the program. The results of this study and interviewee recommendations for program improvement are especially important to help patients who cannot access in-person care during health pandemics, those in rural and remote communities, and to provide support to those awaiting in-person care.

Social Determinants of Health Associated With the Development of Sepsis in Adults: A Scoping Review.

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.

Diagnostic and prognostic accuracy of Protein C in adult patients with sepsis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Sepsis 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. OBJECTIVES: To evaluate the diagnostic accuracy and prognostic strength of PC as a biomarker for adult sepsis. METHODS AND ANALYSIS: Medline, 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 DISSEMINATION: Given 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 NUMBER: CRD42021229786.