International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Open source and reproducible and inexpensive infrastructure for data challenges and education.

Data sharing is necessary to maximize the actionable knowledge generated from research data. Data challenges can encourage secondary analyses of datasets. Data challenges in biomedicine often rely on advanced cloud-based computing infrastructure and expensive industry partnerships. Examples include challenges that use Google Cloud virtual machines and the Sage Bionetworks Dream Challenges platform. Such robust infrastructures can be financially prohibitive for investigators without substantial resources. Given the potential to develop scientific and clinical knowledge and the NIH emphasis on data sharing and reuse, there is a need for inexpensive and computationally lightweight methods for data sharing and hosting data challenges. To fill that gap, we developed a workflow that allows for reproducible model training, testing, and evaluation. We leveraged public GitHub repositories, open-source computational languages, and Docker technology. In addition, we conducted a data challenge using the infrastructure we developed. In this manuscript, we report on the infrastructure, workflow, and data challenge results. The infrastructure and workflow are likely to be useful for data challenges and education.

Clinical decision support tools for paediatric sepsis in resource-poor settings: an international qualitative study.

OBJECTIVE: New paediatric sepsis criteria are being developed by an international task force. However, it remains unknown what type of clinical decision support (CDS) tools will be most useful for dissemination of those criteria in resource-poor settings. We sought to design effective CDS tools by identifying the paediatric sepsis-related decisional needs of multidisciplinary clinicians and health system administrators in resource-poor settings. DESIGN: Semistructured qualitative focus groups and interviews with 35 clinicians (8 nurses, 27 physicians) and 5 administrators at health systems that regularly provide care for children with sepsis, April-May 2022. SETTING: Health systems in Africa, Asia and Latin America, where sepsis has a large impact on child health and healthcare resources may be limited. PARTICIPANTS: Participants had a mean age of 45 years, a mean of 15 years of experience, and were 45% female. RESULTS: Emergent themes were related to the decisional needs of clinicians caring for children with sepsis and to the needs of health system administrators as they make decisions about which CDS tools to implement. Themes included variation across regions and institutions in infectious aetiologies of sepsis and available clinical resources, the need for CDS tools to be flexible and customisable in order for implementation to be successful, and proposed features and format of an ideal paediatric sepsis CDS tool. CONCLUSION: Findings from this study will directly contribute to the design and implementation of CDS tools to increase the uptake and impact of the new paediatric sepsis criteria in resource-poor settings.

Promoting Breast Cancer Surveillance: The EMPOWER Study, a Randomized Clinical Trial in the Childhood Cancer Survivor Study.

PURPOSE: The aim of the current study was to increase the uptake of screening mammography among high-risk women who were treated for a childhood cancer with chest radiotherapy. PATIENTS AND METHODS: Two hundred four female survivors in the Childhood Cancer Survivor Study who were treated with chest radiotherapy with 20 Gy or greater, age 25 to 50 years, and without breast imaging in the past 24 months were randomly assigned 2:1 to receive a mailed informational packet followed by a tailored telephone-delivered brief motivational interview (intervention) versus an attention control. Primary outcome was the difference in the proportion of participants who completed a screening mammogram by 12 months as evaluated in an intent-to-treat analysis. Stratum-adjusted relative risk (RR) and 95% CI were estimated using the Cochran-Mantel-Haenszel method. Secondary outcomes included the completion of screening breast magnetic resonance imaging (MRI) and barriers to screening and moderating factors. RESULTS: Women in the intervention group were significantly more likely than those in the control group to report a mammogram (45 [33.1%] of 136 v 12 [17.6%] of 68; RR, 1.9; 95% CI, 1.1 to 3.3). The intervention was more successful among women age 25 to 39 years (RR, 2.2; 95% CI, 1.1 to 4.7) than among those age 40 to 50 years (RR, 1.4; 95% CI, 0.6 to 3.2). The proportion of women who reported a breast MRI at 12 months was similar between the two groups: 16.2% (intervention) compared with 13.2% (control; RR, 1.2; 95% CI, 0.6 to 2.5). Primary barriers to completing a screening mammogram and/or breast MRI included lack of physician recommendation, deferred action by survivor, cost, and absence of symptoms. CONCLUSION: Use of mailed materials followed by telephone-delivered counseling increased mammography screening rates in survivors at high risk for breast cancer; however, this approach did not increase the rate of breast MRI. Cost of imaging and physician recommendation were important barriers that should be addressed in future studies.